Brain Endothelial Cell Expression Patterns

Abstract
To gain a better understanding of brain tumor angiogenesis, new techniques for isolating brain endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from brain ECS derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed genes that were specifically elevated in tumor-associated brain endothelium. These results confirm that neoplastic and normal endothelium in human brains are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.
Description
TECHNICAL FIELD OF THE INVENTION

This invention is related to the area of angiogenesis and anti-angiogenesis. In particular, it relates to genes which are characteristically expressed in brain glioma endothelial cells.


BACKGROUND OF THE INVENTION

Brain cancers represent an infrequent but deadly form of cancer that has seen little improvement in survivability over the last 30 years. Tumor excision followed by therapies relying on outdated cytotoxins and radiation inevitably results in a diminished quality of life. Gliomas represent the most common brain neoplasms with highly vascular and invasive characteristics defining gliomas as one of the most aggressive tumors known. Classifications of gliomas derive from both the cellular origin and staged aggressiveness. Derived from either astrocytes or oligodendrocytes, astrocytomas and oligodendrogliomas constitute the most common types of gliomas. As is common to other tumor type classifications, glioma increases in aggressiveness from the first to third stages of disease with stage IV, gliobastoma multiforme, being the most aggressive. Moreover, glioblastoma tumors constitute one of the most vascular tumors known.


Vascular permeability within the brain is limited in comparison to other organs. Similarly, the accessibility of brain malignancies to immune surveillance was thought to be restricted as well although more recent evidence suggests the brain is not wholly immunologically privileged. This so called “blood-brain barrier” is thought to derive primarily from a combination of brain-specific capillary transport systems and astrocyte-regulated cross-talk with the endothelial cell-based vasculature (for reviews, see Bart, J., Groen, H. J., Hendrikse, N. H., van der Graaf, W. T., Vaalburg, W., and de Vries, E. G. (2000). The blood-brain barrier and oncology: new insights into function and modulation. Cancer Treat Rev 26, 449-62.) The presence of tight junctions and an observed high electrical resistance both contribute to restricted transvascular molecular exchange. The existence of a therapeutically impermeable vasculature has resulted in a comparatively limited amount of work aimed at intervening in brain malignancies and other CNS diseases. Defining proteins preferentially expressed on either normal or diseased brain endothelial cells holds promise for expanding CNS therapeutic regimens.


The vascular microenvironment within gliomas has been studied primarily through morphological, circulatory and perfusion based experiments (for review see Vajkoczy, P., and Menger, M. D. (2000). Vascular microenvironment in gliomas. J Neurooncol 50, 99-108; and Bart, J., Groen, H. J., Hendrikse, N. H., van der Graaf, W. T., Vaalburg, W., and de Vries, E. G. (2000). The blood-brain barrier and oncology: new insights into function and modulation. Cancer Treat Rev 26, 449-62.) These studies demonstrate profound changes in vascualture architecture associated with tumor progression. Increased fenestrations, malperfusion, hyperpermeability, and reduced leukocyte-EC interaction are all phenotypic observations linked to glioma microvasculature Bernsen, H. J., Rijken, P. F., Oostendorp, T., and van der Kogel, A. J. (1995). Vascularity and perfusion of human gliomas xenografted in the athymic nude mouse. Br J Cancer 71, 721-6; Vick, N. A., and Bigner, D. D. (1972). Microvascular abnormalities in virally-induced canine brain tumors. Structural bases for altered blood-brain barrier function. J Neurol Sci 17, 29-39; and Hobbs, S. K., Monsky, W. L., Yuan, F., Roberts, W. G., Griffith, L., Torchilin, V. P., and Jain, R. K. (1998). Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA 95, 4607-12. It is also suggested that higher grade gliomas utilize intussuceptive capillary growth to a much larger degree than earlier staged gliomas that primarily utilize both sprouting an cooption to advance vessel growth. Vajkoczy, P., Schilling, L., Ullrich, A., Schmiedek, P., and Menger, M. D. (1998). Characterization of angiogenesis and microcirculation of high-grade glioma: an intravital multifluorescence microscopic approach in the athymic nude mouse. J Cereb Blood Flow Metab 18, 510-20. The molecular characterization of glioma ECs has thus far been limited to the evaluation of common growth factors or previously defined brain EC transporters. Holash, J., Maisonpierre, P. C., Compton, D., Boland, P., Alexander, C. R., Zagzag, D., Yancopoulos, G. D., and Wiegand, S. J. (1999). Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284, 1994-8; Guerin, C., Wolff, J. E., Laterra, J., Drewes, L. R., Brem, H., and Goldstein, G. W. (1992). Vascular differentiation and glucose transporter expression in rat gliomas: effects of steroids. Aim Neurol 31, 481-7.


To date, global gene expression profiles from endothelial cell-specific populations is limited to normal and tumorigenic colon tissue. St Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K. E., Montgomery, E., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., and Kinzler, K. W. (2000). Genes expressed in human tumor endothelium. Science 289, 1197-202. There is a need in the art for analysis of endothelial cells from other tissue, so that diagnostic and therapeutic for non-colonic tumors can be developed.


SUMMARY OF THE INVENTION

According to one embodiment of the invention a method is provided to aid in diagnosing glioma. An expression product of at least one gene in a first brain tissue sample suspected of being neoplastic is detected. The at least one gene is selected from the group consisting of signal sequence receptor, delta (translocon-associated protein delta); DC2 protein; KIAA0404 protein; symplekin; Huntingtin interacting protein I; plasmalemma vesicle associated protein; KIAA0726 gene product; latexin protein; transforming growth factor, beta 1; hypothetical protein FLJ22215; Rag C protein; hypothetical protein FLJ23471; N-myristoyltransferase 1; hypothetical protein dJ1181N3.1; ribosomal protein L27; secreted protein, acidic, cysteine-rich (osteonectin); Hs 111988; Hs 112238; laminin, alpha 5; protective protein for beta-galactosidase (galactosialidosis); Melanoma associated gene; Melanoma associated gene; E3 ubiquitin ligase SMURF1; collagen, type N, alpha 1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; gene predicted from cDNA with a complete coding sequence; Thy-1 cell surface antigen; Hs 127824; GTP binding protein 2; Homo sapiens mRNA; cDNA DKFZp586D0918 (from clone DKFZp586D0918); cutaneous T-cell lymphoma-associated tumor antigen se20-4; differentially expressed nucleolar TGF-beta1 target protein (DENTT); dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); smoothelin; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); putative translation initiation factor; retinoic acid induced 14; matrix metalloproteinase 9 (gelatinase B, 92 kD gelatinase, 92 kD type IV collagenase); Lutheran blood group (Auberger b antigen included); stanniocalcin 2; nuclear factor (erythroid-derived 2)-like 2; protein tyrosine phosphatase, non-receptor type 1; integrin, alpha 10; collagen, type VI, alpha 2; chromosome 21 open reading frame 25; CDC37 (cell division cycle 37, S. cerevisiae, homolog); Hs 16450; Rho guanine nucleotide exchange factor (GEF) 7; creatine kinase, brain; hypothetical protein FLJ10297; hypothetical protein FLJ10350; TNF-induced protein; tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein); cofilin 1 (non-muscle); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); v-ets avian erythroblastosis virus E26 oncogene homolog 1; protease, cysteine, 1 (legumain); ribosomal protein L13; chromosome 22 open reading frame 5; zinc finger protein 144 (Mel-18); degenerative spermatocyte (homolog Drosophila; lipid desaturase); eukaryotic translation initiation factor 2C, 2; mitochondrial ribosomal protein 145; prostate tumor over expressed gene 1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (14.5 kD, B14.5a); glioma endothelial marker 1 precursor; NS1-binding protein; ribosomal protein L38; tuftelin-interacting protein; HLA class II region expressed gene KE2; translocase of inner mitochondrial membrane 17 homolog A (yeast); sudD (suppressor of bimD6, Aspergillus nidulans) homolog; heparan sulfate proteoglycan 2 (perlecan); SEC24 (S. cerevisiae) related gene family, member A; NADH dehydrogenase (ubiquinone) Fe—S protein 7 (20 kD) (NADH-coenzyme Q reductase); DNA segment on chromosome X and Y (unique) 155 expressed sequence; annexin A2; Homo sapiens clone 24670 mRNA sequence; hypothetical protein; matrix metalloproteinase 10 (stromelysin 2); KIAA 1049 protein; G protein-coupled receptor; hypothetical protein FLJ20401; matrix metalloproteinase 14 (membrane-inserted); KIAA0470 gene product; solute carrier family 29 (nucleoside transporters), member 1; stanniocalcin 1; stanniocalcin 1; stanniocalcin 1; tumor suppressor deleted in oral cancer-related 1; tumor suppressor deleted in oral cancer-related 1; apolipoprotein C—I; glutathione peroxidase 4 (phospholipid hydroperoxidase); Hs 272106; transcription factor binding to IGHM enhancer 3; hypothetical protein DKFZp762A227; hypothetical protein FLJ22362; CD59 antigen p18-20 (antigen identified by monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344); PRO0628 protein; melanoma-associated antigen recognised by cytotoxic T lymphocytes; LOC88745; Homo sapiens beta-1,3-galactosyltransferase-6 (B3GALT6) mRNA, complete cds; sprouty (Drosophila) homolog 4; sprouty (Drosophila) homolog 4; Homo sapiens mRNA; cDNA DKFZp434E1515 (from clone DKFZp434E1515); coactosin-like protein; hypothetical protein FLJ21865; Hs296234; KIAA0685 gene product; hypothetical protein FLJ10980; ribosomal protein L10; ribosomal protein S19; Hs 299251; Huntingtin interacting protein K; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 50374; Hs 311780; Hs 212191; v-akt murine thymoma viral oncogene homolog 2; Hs 328774; transducin-like enhancer of split 2, homolog of Drosophila E(sp1); KIAA1870 protein; ribosomal protein L10a; peptidylprolyl isomerase A (cyclophilin A); Hs 344224; hypothetical protein FLJ23239; hypothetical protein DKFZp761H221; KIAA1887 protein; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 701679; Homo sapiens cDNA FLJ30634 fis, clone CTONG2002453; Homo sapiens cDNA FLJ32203 fis, clone PLACE6003038, weakly similar to ZINC FINGER PROTEIN 84; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1035904; hypothetical protein L0057333; myosin ID; plexin B2; lectin, galactoside-binding, soluble, 8 (galectin 8); double ring-finger protein, Dorfin; DKFZP434B168 protein; LIM domain binding 2; integrin beta 4 binding protein; synaptopodin; Hs 54828; insulin induced gene 1; acetyl LDL receptor; SREC; excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence); hypothetical protein FLJ22329; schwannomin-interacting protein 1; PTEN induced putative kinase 1; myosin X; Homo sapiens cDNA FLJ32424 fis, clone SKMUS2000954, moderately similar to Homo sapiens F-box protein Fbx25 (FBX25) 97; golgi phosphoprotein 1; splicing factor, arginine/serine-rich 6; laminin, gamma 3; cysteine-rich protein 2; U6 snRNA-associated Sm-like protein LSm7; hypothetical protein FLJ10707; Homo sapiens, Similar to RIKEN cDNA 2310012N15 gene, clone IMAGE:3342825, mRNA, partial cds; macrophage migration inhibitory factor (glycosylation-inhibiting factor); ubiquinol-cytochrome c reductase hinge protein; gap junction protein, alpha 1, 43 kD (connexin 43); dihydropyrimidinase-like 3; aquaporin 1 (channel-forming integral protein, 28 kD); protein expressed in thyroid; macrophage myristoylated alanine-rich C kinase substrate; procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI); protease, serine, 11 (IGF binding); 24-dehydrocholesterol reductase; collagen, type IV, alpha 2; profilin 1; apolipoprotein D; hyaluronoglucosaminidase 2; hypothetical protein FLJ22678; quiescin Q6; ras homolog gene family, member A; ras homolog gene family, member A; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; uridine phosphorylase; KIAA0638 protein; B7 homolog 3; lamin A/C; lamin A/C; lamin A/C; regulator of G-protein signalling 12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8; Homo sapiens, Similar to RIKEN cDNA 5730528L13 gene, clone MGC:17337 IMAGE:4213591, mRNA, complete cds; prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy); laminin, alpha 4; transcription elongation factor A (SII), 1; lectin, galactoside-binding, soluble, 3 binding protein; ribosomal protein S16; glycophorin C (Gerbich blood group); endothelin receptor type B; serine (or cysteine) proteinase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1; biglycan; small nuclear ribonucleoprotein polypeptide B″; transmembrane 4 superfamily member 2; TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28 kD; lysyl oxidase-like 2; SRY (sex determining region Y)-box 4; SOX4 SRY (sex determining region Y)-box 4; SRY (sex determining region Y)-box 4; actin related protein 2/3 complex, subunit 2 (34 kD); Homo sapiens cDNA: FLJ23507 fis, clone LNG03128; hypothetical protein FLJ12442; Fas (TNFRSF6)-associated via death domain; mitogen-activated protein kinase kinase kinase 11; TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal); insulin receptor; cell membrane glycoprotein, 110000M(r) (surface antigen); Homo sapiens cDNA FLJ11863 fis, clone HEMBA1006926; jagged 1 (Alagille syndrome); KIAA0304 gene product; pre-B-cell leukemia transcription factor 2; Homo sapiens cDNA FLJ31238 fis, clone KIDNE2004864; p53-induced protein; complement component 1, q subcomponent, receptor 1; complement component 1, q subcomponent, receptor 1; apolipoprotein E; chemokine (C—C motif) ligand 3; coagulation factor II (thrombin) receptor-like 3; coagulation factor III (thromboplastin, tissue factor); collagen, type I, alpha 1; collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant); C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; cystatin C (amyloid angiopathy and cerebral hemorrhage); endoplasmic reticulum associated protein 140 kDa; ESTs; ESTs; ESTs, Highly similar to hypothetical protein FLJ10350 [Homo sapiens] [H.sapiens]; ESTs, Highly similar to ITB1_HUMAN Integrin beta-1 precursor (Fibronectin receptor beta subunit) (CD29) (Integrin VLA-4 beta subunit) [H.sapiens]; ESTs, Weakly similar to hypothetical protein FLJ20489 [Homo sapiens] [H.sapiens]; ESTs, Weakly similar to T17346 hypothetical protein DKFZp586O1624.1—human (fragment) [H.sapiens]; ESTs, Weakly similar to T21371 hypothetical protein F25H8.3—Caenorhabditis elegans [C.elegans]; eukaryotic translation initiation factor 4A, isoform 1; heme oxygenase (decycling) 1; Hermansky-Pudlak syndrome 4; Homo sapiens cDNA FLJ34888 fis, clone NT2NE2017332; Homo sapiens cDNA FLJ39848 fis, clone SPLEN2014669; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1977059; Homo sapiens, clone IMAGE:4845226, mRNA; hypothetical protein FLJ22329; hypothetical protein FLJ32205; hypothetical protein MGC4677; inhibin, beta B (activin AB beta polypeptide); insulin-like growth factor binding protein 5; junction plakoglobin; KIAA0620 protein; KIAA0943 protein; likely ortholog of rat vacuole membrane protein 1; Lysosomal-associated multispanning membrane protein-5; major histocompatibility complex, class I, B; major histocompatibility complex, class I, C; matrix Gla protein; matrix metalloproteinase 1 (interstitial collagenase); microtubule-associated protein 1 light chain 3 beta; nerve growth factor receptor (TNFR superfamily, member 16); ribosomal protein S9; ring finger protein 40; S100 calcium binding protein, beta (neural); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; SPARC-like 1 (mast9, hevin); tumor necrosis factor, alpha-induced protein 3; UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 3; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5; von Willebrand factor; v-akt murine thymoma vial oncogene homolog 2; cyclin-dependent kinase (cdc2-like) 10; ortholog mouse myocytic induction/differentiation originator; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16); insulin-like growth factor binding protein; leukemia inhibitory factor; protein tyrosine phosphatase, nonreceptor type I; and Homo sapiens, clone IMAGE:3908182, mRNA, partial cds. Expression of the at least one gene in the first brain tissue sample is compared to expression of the at least one gene in a second brain tissue sample which is normal. Increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample identifies the first brain tissue sample as likely to be neoplastic. According to another embodiment of the invention a method is provided of treating a glioma. Cells of the glioma are contacted with an antibody. The antibody specifically binds to an extracellular epitope of a protein selected from the group consisting of plasmalemma associated protein; KIAA0726 gene product; osteonectin: laminin, alpha 5; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; Thy-1 cell surface antigen; dysferlin, limb girdle muscular dystrophy 2B; integrin, alpha 5; matrix metalloproteinase 9; Lutjheran blood group, integrink, alpha 10, collagen, type VI, alpha 2; glioma endothelial marker 1 precursor; translocase of inner mitochondrial membrane 17 homolog A; heparan sulfate proteoglycan 2; annexin A2; matrix metalloproteinase 10; G protein-coupled receptor; matrix metalloproteinase 14; solute carrier family 29, member 1; CD59 antigen p18-20; KIAA 1870 protein; plexin B2; lectin, glactoside-binding, soluble, 8; integrin beta 4 binding protein; acetyl LDL receptor; laminin, gamma 3; macrophage migration inhibitory factor; gap junction protein, alpha 1, 43 kD; aquaporin 1; protease, serine, 11; collagen, type IV, alpha 2; apolipoprotein D; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; regulator of G-protein signaling 12; prosaposin; laminin, alpha 4; lectin, galactoside-binding, soluble, 3 binding protein; glycophorin C; endothelin receptor type B; biglycan; transmembrane 4 superfamily member 2; lysyl osidase-like 2; TEK tyrosine kinase, endothelial; insulin receptore; cell membrane glycoprotein, 110000M(r); jagged 1; plasmalemma vesicle associated protein; TEM13, Thy-1 cell surface antigen; coagulation factor II (thrombin) receptor-like 3; dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); likely ortholog of rat vacuole membrane protein 1; nerve growth factor receptor (TNFR superfamily, member 16); degenerative spermatocyte homolog, lipid desaturase (Drosophila); TEM1, endosialin; heme oxygenase (decycling) 1; G protein-coupled receptor; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; matrix metalloproteinase 14 (membrane-inserted); solute carrier family 29 (nucleoside transporters), member 1; likely ortholog of mouse embryonic epithelial gene 1; major histocompatibility complex, class I, C; likely ortholog of mouse fibronectin type III repeat containing protein 1; sprouty homolog 4 (Drosophila); KIAA0620 protein; coagulation factor III (thromboplastin, tissue factor); aquaporin 1 (channel-forming integral protein, 28 kDa); major histocompatibility complex, class I, B; Lysosomal-associated multispanning membrane protein-5; endothelin receptor type B; insulin receptor; complement component 1, q subcomponent, receptor 1; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16) and complement component 1, q subcomponent, receptor 1. Immune destruction of cells of the glioma is thereby triggered.


According to still another embodiment of the invention a method is provided for identifying a test compound as a potential anti-cancer or anti-glioma drug. A test compound is contacted with a cell which expresses at least one gene selected from the group consisting of: signal sequence receptor, delta (translocon-associated protein delta); DC2 protein; KIAA0404 protein; symplekin; Huntingtin interacting protein I; plasmalemma vesicle associated protein; KIAA0726 gene product; latexin protein; transforming growth factor, beta 1; hypothetical protein FLJ22215; Rag C protein; hypothetical protein FLJ23471; N-myristoyltransferase 1; hypothetical protein dJ1181N3.1; ribosomal protein L27; secreted protein, acidic, cysteine-rich (osteonectin); Hs 111988; Hs 112238; laminin, alpha 5; protective protein for beta-galactosidase (galactosialidosis); Melanoma associated gene; Melanoma associated gene; E3 ubiquitin ligase SMURF1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; gene predicted from cDNA with a complete coding sequence; Thy-1 cell surface antigen; Hs 127824; GTP binding protein 2; Homo sapiens mRNA; cDNA DKFZp586D0918 (from clone DKFZp586D0918); cutaneous T-cell lymphoma-associated tumor antigen se20-4; differentially expressed nucleolar TGF-beta1 target protein (DENTT); dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); smoothelin; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); putative translation initiation factor; retinoic acid induced 14; matrix metalloproteinase 9 (gelatinase B, 92 kD gelatinase, 92 kD type IV collagenase); Lutheran blood group (Auberger b antigen included); stanniocalcin 2; nuclear factor (erythroid-derived 2)-like 2; protein tyrosine phosphatase, non-receptor type 1; integrin, alpha 10; collagen, type VI, alpha 2; chromosome 21 open reading frame 25; CDC37 (cell division cycle 37, S. cerevisiae, homolog); Hs 16450; Rho guanine nucleotide exchange factor (GEF) 7; creatine kinase, brain; hypothetical protein FLJ10297; hypothetical protein FLJ10350; TNF-induced protein; tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein); cofilin 1 (non-muscle); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); v-ets avian erythroblastosis virus E26 oncogene homolog 1; protease, cysteine, 1 (legumain); ribosomal protein L13; chromosome 22 open reading frame 5; zinc finger protein 144 (Mel-18); degenerative spermatocyte (homolog Drosophila; lipid desaturase); eukaryotic translation initiation factor 2C, 2; mitochondrial ribosomal protein L45; prostate tumor over expressed gene 1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (14.5 kD, B 14.5a); glioma endothelial marker 1 precursor; NS1-binding protein; ribosomal protein L38; tuftelin-interacting protein; HLA class II region expressed gene KE2; translocase of inner mitochondrial membrane 17 homolog A (yeast); sudD (suppressor of bimD6, Aspergillus nidulans) homolog; heparan sulfate proteoglycan 2 (perlecan); SEC24 (S. cerevisiae) related gene family, member A; NADH dehydrogenase (ubiquinone) Fe—S protein 7 (20 kD) (NADH-coenzyme Q reductase); DNA segment on chromosome X and Y (unique) 155 expressed sequence; annexin A2; Homo sapiens clone 24670 mRNA sequence; hypothetical protein; matrix metalloproteinase 10 (stromelysin 2); KIAA1049 protein; G protein-coupled receptor; hypothetical protein FLJ20401; matrix metalloproteinase 14 (membrane-inserted); KIAA0470 gene product; solute carrier family 29 (nucleoside transporters), member 1; stanniocalcin 1; stanniocalcin 1; stanniocalcin 1; tumor suppressor deleted in oral cancer-related 1; tumor suppressor deleted in oral cancer-related 1; apolipoprotein C—I; glutathione peroxidase 4 (phospholipid hydroperoxidase); Hs 272106; transcription factor binding to IGHM enhancer 3; hypothetical protein DKFZp762A227; hypothetical protein FLJ22362; CD59 antigen p18-20 (antigen identified by monoclonal antibodies 16.3A5, EJ16, 030, EL32 and G344); PRO0628 protein; melanoma-associated antigen recognised by cytotoxic T lymphocytes; LOC88745; Homo sapiens beta-1,3-galactosyltransferase-6 (B3GALT6) mRNA, complete cds; sprouty (Drosophila) homolog 4; sprouty (Drosophila) homolog 4; Homo sapiens mRNA; cDNA DKFZp434E1515 (from clone DKFZp434E1515); coactosin-like protein; hypothetical protein FLJ21865; Hs296234; KIAA0685 gene product; hypothetical protein FLJ10980; ribosomal protein L10; ribosomal protein S19; Hs 299251; Huntingtin interacting protein K; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 50374; Hs 311780; Hs 212191; v-akt murine thymoma viral oncogene homolog 2; Hs 328774; transducin-like enhancer of split 2, homolog of Drosophila E(sp1); KIAA1870 protein; ribosomal protein L10a; peptidylprolyl isomerase A (cyclophilin A); Hs 344224; hypothetical protein FLJ23239; hypothetical protein DKFZp761H221; KIAA1887 protein; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 701679; Homo sapiens cDNA F1130634 fis, clone CTONG2002453; Homo sapiens cDNA FLJ32203 fis, clone PLACE6003038, weakly similar to ZINC FINGER PROTEIN 84; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1035904; hypothetical protein L0057333; myosin ID; plexin B2; lectin, galactoside-binding, soluble, 8 (galectin 8); double ring-finger protein, Dorfin; DKFZP434B168 protein; LIM domain binding 2; integrin beta 4 binding protein; synaptopodin; Hs 54828; insulin induced gene 1; acetyl LDL receptor; SREC; excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence); hypothetical protein FLJ22329; schwannomin-interacting protein 1; PTEN induced putative kinase 1; myosin X; Homo sapiens cDNA FLJ32424 fis, clone SKMUS2000954, moderately similar to Homo sapiens F-box protein Fbx25 (FBX25) 97; golgi phosphoprotein 1; splicing factor, arginine/serine-rich 6; laminin, gamma 3; cysteine-rich protein 2; U6 snRNA-associated Sm-like protein LSm7; hypothetical protein FLJ10707; Homo sapiens, Similar to RIKEN cDNA 2310012N15 gene, clone IMAGE:3342825, mRNA, partial cds; macrophage migration inhibitory factor (glycosylation-inhibiting factor); ubiquinol-cytochrome c reductase hinge protein; gap junction protein, alpha 1, 43 kD (connexin 43); dihydropyrimidinase-like 3; aquaporin 1 (channel-forming integral protein, 28 kD); protein expressed in thyroid; macrophage myristoylated alanine-rich C kinase substrate; procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI); protease, serine, 11 (IGF binding); 24-dehydrocholesterol reductase; collagen, type IV, alpha 2; profilin 1; apolipoprotein D; hyaluronoglucosaminidase 2; hypothetical protein FLJ22678; quiescin Q6; ras homolog gene family, member A; ras homolog gene family, member A; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; uridine phosphorylase; KIAA0638 protein; B7 homolog 3; lamin A/C; lamin A/C; lamin A/C; regulator of G-protein signalling 12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8; Homo sapiens, Similar to RIKEN cDNA 5730528L13 gene, clone MGC:17337 IMAGE:4213591, mRNA, complete cds; prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy); laminin, alpha 4; transcription elongation factor A (SII), 1; lectin, galactoside-binding, soluble, 3 binding protein; ribosomal protein S16; glycophorin C (Gerbich blood group); endothelin receptor type B; serine (or cysteine) proteinase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1; biglycan; small nuclear ribonucleoprotein polypeptide B″; transmembrane 4 superfamily member 2; TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28 kD; lysyl oxidase-like 2; SRY (sex determining region Y)-box 4; SOX4 SRY (sex determining region Y)-box 4; SRY (sex determining region Y)-box 4; actin related protein 2/3 complex, subunit 2 (34 kD); Homo sapiens cDNA: FLJ23507 fis, clone LNG03128; hypothetical protein FLJ12442; Fas (TNFRSF6)-associated via death domain; mitogen-activated protein kinase kinase kinase 11; TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal); insulin receptor; cell membrane glycoprotein, 110000M(r) (surface antigen); Homo sapiens cDNA FLJ11863 fis, clone HEMBA1006926; jagged 1 (Alagille syndrome); KIAA0304 gene product; pre-B-cell leukemia transcription factor 2; Homo sapiens cDNA FLJ31238 fis, clone KIDNE2004864; p53-induced protein; complement component 1, q subcomponent, receptor 1; complement component 1, q subcomponent, receptor 1; apolipoprotein E; chemokine (C—C motif) ligand 3; coagulation factor II (thrombin) receptor-like 3; coagulation factor III (thromboplastin, tissue factor); collagen, type I, alpha 1; collagen, type IR, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant); C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; cystatin C (amyloid angiopathy and cerebral hemorrhage); endoplasmic reticulum associated protein 140 kDa; ESTs; ESTs; ESTs, Highly similar to hypothetical protein FLJ10350 [Homo sapiens] [H.sapiens]; ESTs, Highly similar to ITB1 HUMAN Integrin beta-1 precursor (Fibronectin receptor beta subunit) (CD29) (Integrin VLA-4 beta subunit) [H.sapiens]; ESTs, Weakly similar to hypothetical protein FLJ20489 [Homo sapiens] [H.sapiens]; ESTs, Weakly similar to T17346 hypothetical protein DKFZp586O1624.1-human (fragment) [H.sapiens]; ESTs, Weakly similar to T21371 hypothetical protein F25H8.3—Caenorhabditis elegans [C.elegans]; eukaryotic translation initiation factor 4A, isoform 1; heme oxygenase (decycling) 1; Hermansky-Pudlak syndrome 4; Homo sapiens cDNA FLJ34888 fis, clone NT2NE2017332; Homo sapiens cDNA FLJ39848 fis, clone SPLEN2014669; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1977059; Homo sapiens, clone IMAGE:4845226, mRNA; hypothetical protein FLJ22329; hypothetical protein FLJ32205; hypothetical protein MGC4677; inhibin, beta B (activin AB beta polypeptide); insulin-like growth factor binding protein 5; junction plakoglobin; KIAA0620 protein; KIAA0943 protein; likely ortholog of rat vacuole membrane protein 1; Lysosomal-associated multispanning membrane protein-5; major histocompatibility complex, class I, B; major histocompatibility complex, class I, C; matrix Gla protein; matrix metalloproteinase 1 (interstitial collagenase); microtubule-associated protein 1 light chain 3 beta; nerve growth factor receptor (TNFR superfamily, member 16); ribosomal protein S9; ring finger protein 40; S100 calcium binding protein, beta (neural); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; SPARC-like 1 (mast9, hevin); tumor necrosis factor, alpha-induced protein 3; UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 3; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5; von Willebrand factor; v-akt murine thymoma vial oncogene homolog 2; cyclin-dependent kinase (cdc2-like) 10; ortholog mouse myocytic induction/differentiation originator; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16); insulin-like growth factor binding protein; leukemia inhibitory factor; protein tyrosine phosphatase, nonreceptor type I; and Homo sapiens, clone IMAGE:3908182, mRNA, partial cds. An expression product of the at least one gene is monitored. The test compound is identified as a potential anti-cancer drug if it decreases the expression of the at least one gene.


According to yet another embodiment of the invention a method is provided to aid in diagnosing glioma. An mRNA of at least one gene in a first brain tissue sample suspected of being neoplastic is detected. The at least one gene is identified by a tag selected from the group consisting of SEQ ID NO: 1-32. Expression of the at least one gene in the first brain tissue sample is compared to expression of the at least one gene in a second brain tissue sample which is normal. If increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample if found, the first brain tissue sample is identified as likely to be neoplastic.


Another embodiment of the invention is a method of identifying a test compound as a potential anti-cancer or anti-glioma drug. A test compound is contacted with a cell. The cell expresses an mRNA of at least one gene identified by a tag selected from the group consisting of SEQ ID NO: 1-32. An mRNA of the at least one gene is monitored. The test compound is identified as a potential anti-cancer drug if it decreases the expression of at least one gene.


Still another embodiment of the invention is a method to induce an immune response to glioma. A protein or nucleic acid encoding a protein is administered to a mammal, preferably a human. The protein is selected from the group consisting of: signal sequence receptor, delta (translocon-associated protein delta); DC2 protein; KIAA0404 protein; symplekin; Huntingtin interacting protein I; plasmalemma vesicle associated protein; KIAA0726 gene product; latexin protein; transforming growth factor, beta 1; hypothetical protein FLJ22215; Rag C protein; hypothetical protein FLJ23471; N-myristoyltransferase 1; hypothetical protein dJ1181N3.1; ribosomal protein L27; secreted protein, acidic, cysteine-rich (osteonectin); Hs 111988; Hs 112238; laminin, alpha 5; protective protein for beta-galactosidase (galactosialidosis); Melanoma associated gene; Melanoma associated gene; E3 ubiquitin ligase SMURF1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; gene predicted from cDNA with a complete coding sequence; Thy-1 cell surface antigen; Hs 127824; GTP binding protein 2; Homo sapiens mRNA; cDNA DKFZp586D0918 (from clone DKFZp586D0918); cutaneous T-cell lymphoma-associated tumor antigen se20-4; differentially expressed nucleolar TGF-beta1 target protein (DENTT); dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); smoothelin; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); putative translation initiation factor; retinoic acid induced 14; matrix metalloproteinase 9 (gelatinase B, 92 kD gelatinase, 92 kD type IV collagenase); Lutheran blood group (Auberger b antigen included); stanniocalcin 2; nuclear factor (erythroid-derived 2)-like 2; protein tyrosine phosphatase, non-receptor type 1; integrin, alpha 10; collagen, type VI, alpha 2; chromosome 21 open reading frame 25; CDC37 (cell division cycle 37, S. cerevisiae, homolog); Hs 16450; Rho guanine nucleotide exchange factor (GEF) 7; creatine kinase, brain; hypothetical protein FLJ10297; hypothetical protein FLJ10350; TNF-induced protein; tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein); cofilin 1 (non-muscle); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); v-ets avian erythroblastosis virus E26 oncogene homolog 1; protease, cysteine, 1 (legumain); ribosomal protein L13; chromosome 22 open reading frame 5; zinc finger protein 144 (Mel-18); degenerative spermatocyte (homolog Drosophila; lipid desaturase); eukaryotic translation initiation factor 2C, 2; mitochondrial ribosomal protein L45; prostate tumor over expressed gene 1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (14.5 kD, B14.5a); glioma endothelial marker 1 precursor; NS1-binding protein; ribosomal protein L38; tuftelin-interacting protein; HLA class II region expressed gene KE2; translocase of inner mitochondrial membrane 17 homolog A (yeast); sudD (suppressor of bimD6, Aspergillus nidulans) homolog; heparan sulfate proteoglycan 2 (perlecan); SEC24 (S. cerevisiae) related gene family, member A; NADH dehydrogenase (ubiquinone) Fe—S protein 7 (20 kD) (NADH-coenzyme Q reductase); DNA segment on chromosome X and Y (unique) 155 expressed sequence; annexin A2; Homo sapiens clone 24670 mRNA sequence; hypothetical protein; matrix metalloproteinase 10 (stromelysin 2); KIAA1049 protein; G protein-coupled receptor; hypothetical protein FLJ20401; matrix metalloproteinase 14 (membrane-inserted); KIAA0470 gene product; solute carrier family 29 (nucleoside transporters), member 1; stanniocalcin 1; stanniocalcin 1; stanniocalcin 1; tumor suppressor deleted in oral cancer-related 1; tumor suppressor deleted in oral cancer-related 1; apolipoprotein C—I; glutathione peroxidase 4 (phospholipid hydroperoxidase); Hs 272106; transcription factor binding to IGHM enhancer 3; hypothetical protein DKFZp762A227; hypothetical protein FLJ22362; CD59 antigen p18-20 (antigen identified by monoclonal antibodies 163A5, EJ16, EJ30, EL32 and G344); PRO0628 protein; melanoma-associated antigen recognised by cytotoxic T lymphocytes; LOC88745; Homo sapiens beta-1,3-galactosyltransferase-6 (B3GALT6) mRNA, complete cds; sprouty (Drosophila) homolog 4; sprouty (Drosophila) homolog 4; Homo sapiens mRNA; cDNA DKFZp434E1515 (from clone DKFZp434E1515); coactosin-like protein; hypothetical protein FLJ21865; Hs296234; KIAA0685 gene product; hypothetical protein FLJ10980; ribosomal protein L10; ribosomal protein S19; Hs 299251; Huntingtin interacting protein K; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 50374; Hs 311780; Hs 212191; v-akt murine thymoma viral oncogene homolog 2; Hs 328774; transducin-like enhancer of split 2, homolog of Drosophila E(sp1); KIAA1870 protein; ribosomal protein L10a; peptidylprolyl isomerase A (cyclophilin A); Hs 344224; hypothetical protein FLJ23239; hypothetical protein DKFZp761H221; KIAA1887 protein; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 701679; Homo sapiens cDNA FLJ30634 fis, clone CTONG2002453; Homo sapiens cDNA FLJ32203 fis, clone PLACE6003038, weakly similar to ZINC FINGER PROTEIN 84; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1035904; hypothetical protein L0057333; myosin ID; plexin B2; lectin, galactoside-binding, soluble, 8 (galectin 8); double ring-finger protein, Dorfin; DKFZP434B 168 protein; LIM domain binding 2; integrin beta 4 binding protein; synaptopodin; Hs 54828; insulin induced gene 1; acetyl LDL receptor; SREC; excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence); hypothetical protein FLJ22329; schwannomin-interacting protein 1; PTEN induced putative kinase 1; myosin X; Homo sapiens cDNA FLJ32424 fis, clone SKMUS2000954, moderately similar to Homo sapiens F-box protein Fbx25 (FBX25) 97; golgi phosphoprotein 1; splicing factor, arginine/serine-rich 6; laminin, gamma 3; cysteine-rich protein 2; U6 snRNA-associated Sm-like protein LSm7 hypothetical protein FLJ10707; Homo sapiens, Similar to RIKEN cDNA 2310012N15 gene, clone IMAGE:3342825, mRNA, partial cds; macrophage migration inhibitory factor (glycosylation-inhibiting factor); ubiquinol-cytochrome c reductase hinge protein; gap junction protein, alpha 1, 43 kD (connexin 43); dihydropyrimidinase-like 3; aquaporin 1 (channel-forming integral protein, 28 kD); protein expressed in thyroid; macrophage myristoylated alanine-rich C kinase substrate; procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI); protease, serine, 11 (IGF binding); 24-dehydrocholesterol reductase; collagen, type IV, alpha 2; profilin 1; apolipoprotein D; hyaluronoglucosaminidase 2; hypothetical protein FLJ22678; quiescin Q6; ras homolog gene family, member A; ras homolog gene family, member A; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; uridine phosphorylase; KIAA0638 protein; B7 homolog 3; lamin A/C; lamin A/C; lamin A/C; regulator of G-protein signalling 12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8; Homo sapiens, Similar to RIKEN cDNA 5730528L13 gene, clone MGC:17337 IMAGE:4213591, mRNA, complete cds; prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy); laminin, alpha 4; transcription elongation factor A (SII), 1; lectin, galactoside-binding, soluble, 3 binding protein; ribosomal protein S16; glycophorin C (Gerbich blood group); endothelin receptor type B; serine (or cysteine) proteinase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1; biglycan; small nuclear ribonucleoprotein polypeptide B″; transmembrane 4 superfamily member 2; TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28 kD; lysyl oxidase-like 2; SRY (sex determining region Y)-box 4; SOX4 SRY (sex determining region Y)-box 4; SRY (sex determining region Y)-box 4; actin related protein 2/3 complex, subunit 2 (34 kD); Homo sapiens cDNA: FLJ23507 fis, clone LNG03128; hypothetical protein FLJ12442; Fas (TNFRSF6)-associated via death domain; mitogen-activated protein kinase kinase kinase 11; TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal); insulin receptor; cell membrane glycoprotein, 110000M(r) (surface antigen); Homo sapiens cDNA FLJ11863 fis, clone HEMBA1006926; jagged 1 (Alagille syndrome); KIAA0304 gene product; pre-B-cell leukemia transcription factor 2; Homo sapiens cDNA FLJ31238 fis, clone KIDNE2004864; p53-induced protein; complement component 1, q subcomponent, receptor 1; complement component 1, q subcomponent, receptor 1; apolipoprotein E; chemokine (C—C motif) ligand 3; coagulation factor II (thrombin) receptor-like 3; coagulation factor III (thromboplastin, tissue factor); collagen, type I, alpha 1; collagen, type III alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant); C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; cystatin C (amyloid angiopathy and cerebral hemorrhage); endoplasmic reticulum associated protein 140 kDa; ESTs; ESTs; ESTs, Highly similar to hypothetical protein FLJ10350 [Homo sapiens] [H.sapiens]; ESTs, Highly similar to ITB1_HUMAN Integrin beta-1 precursor (Fibronectin receptor beta subunit) (CD29) (Integrin VLA-4 beta subunit) [H.sapiens]; ESTs, Weakly similar to hypothetical protein FLJ20489 [Homo sapiens] [H.sapiens]; ESTs, Weakly similar to T17346 hypothetical protein DKFZp58601624.1-human (fragment) [H.sapiens]; ESTs, Weakly similar to T21371 hypothetical protein F25H8.3—Caenorhabditis elegans [C.elegans]; eukaryotic translation initiation factor 4A, isoform 1; heme oxygenase (decycling) 1; Hermansky-Pudlak syndrome 4; Homo sapiens cDNA FLJ34888 fis, clone NT2NE2017332; Homo sapiens cDNA FLJ39848 fis, clone SPLEN2014669; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1977059; Homo sapiens, clone IMAGE:4845226, mRNA; hypothetical protein FLJ22329; hypothetical protein FLJ32205; hypothetical protein MGC4677; inhibin, beta B (activin AB beta polypeptide); insulin-like growth factor binding protein 5; junction plakoglobin; KIAA0620 protein; KIAA0943 protein; likely ortholog of rat vacuole membrane protein 1; Lysosomal-associated multispanning membrane protein-5; major histocompatibility complex, class I, B; major histocompatibility complex, class I, C; matrix Gla protein; matrix metalloproteinase 1 (interstitial collagenase); microtubule-associated protein 1 light chain 3 beta; nerve growth factor receptor (TNFR superfamily, member 16); ribosomal protein S9; ring finger protein 40; S100 calcium binding protein, beta (neural); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; SPARC-like 1 (mast9, hevin); tumor necrosis factor, alpha-induced protein 3; UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 3; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5; von Willebrand factor; v-akt murine thymoma vial oncogene homolog 2; cyclin-dependent kinase (cdc2-like) 10; ortholog mouse myocytic induction/differentiation originator; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16); insulin-like growth factor binding protein; leukemia inhibitory factor; protein tyrosine phosphatase, nonreceptor type I; and Homo sapiens, clone IMAGE:3908182, mRNA, partial cds. An immune response to the protein is thereby induced.


The present invention thus provides the art with methods of diagnosing and treating gliomas and other brain tumors.







DETAILED DESCRIPTION OF THE INVENTION

Using SAGE (Serial Analysis of Gene Expression) profiling, this study was able to identify previously unrecognized, angiogenesis-specific markers that discriminate between non-proliferative and pathologic endothelial cells. We identified 255 human genes that were expressed at significantly higher levels in brain tumor endothelium than in normal brain endothelium. See Table 1. We have named these markers GEMs (glioma endothelial markers). Any of the GEMs disclosed in any of the tables can be used in the methods of the present invention, according to the discretion of the skilled artisan.


ECs represent only a minor fraction of the total cells within normal or tumor tissues, and only those EC transcripts expressed at the highest levels would be expected to be represented in libraries constructed from unfractionated tissues. The genes described in the current study should therefore provide a valuable resource for basic and clinical studies of human brain angiogenesis in the future. Genes which have been identified as expressed more in glioma endothelial cells than in normal brain endothelial cells (GEMs) include those which correspond to tags shown in SEQ ID NOS: 1-32. The tags correspond to the segment of the cDNA that is 3′ of the 3′ most restriction endonuclease site for the restriction enzyme NlaIII which was used as the anchoring enzyme. The tag shown is the same strand as the mRNA. Other such genes are listed in Tables 1 and 2.














TABLE 1








SEQ




StdTag
SEQ
LongTag
ID
Function




















AAACCATTCT
1
AAACCATTCTCCTCCGC
256







AAGGCAGGGA
2
AAGGCAGGGAGGGAGGG
257





ACACAGCAAG
1
ACACAGCAAGACGAGAA
258





AGCTGGAGTC
4
AGCTGGAGTCCTAGGCA
259





AGCTGGCACC
5
AGCTGGCACCAGAGCCC
260





ATAAATGAGG
6
ATAAATGAGGTAAGGTC
261





CAAGCACCCC
7
CAAGCACCCCCGTTCCA
262





CACTACCCAC
8
CACTACCCACCAGACGC
263





CACTACTCAC
9
CACTACTCACCAGGCGC
264





CCCACCTCCA
10
CCCACCTCCAGTCCAGC
265





CCCGCCTCTT
11
CCCGCCTCTTCACGGGC
266





CCTCAGATGT
12
CCTCAGATGTTTGAAAA
267





CGCTACTCAC
13
CGCTACTCACCAGACGC
268





CTAAGACCTC
14
CTAAGACCTCACCAGTC
269





CTAAGACTTC
15
CTAAGACTTCACCGGTC
270





GAGTGGGTGC
16
GAGTGGGTGCAGCCTCC
271





GGGACAGCTG
17
GGGACAGCTGTCTGTGG
272





GGGTTGGCTT
18
GGGTTGGCTTGAAACCA
273





GTAAGTGTAC
19
GTAAGTGTACTGGAAGT
274





GTAAGTGTAC
20
GTAAGTGTACTGGTAAG
275





GTAAGGGGTAA
21
GTAGGGGTAAAAGGAGG
276





TAACCACTGC
22
TAACCACTGCACTTTCC
277





TACTGCTCGG
23
TACTGCTCGGAGGTCGG
278





TCAGGCTGAA
24
TCAGGCTGAAGTCAGGC
279





TCCATACACC
25
TCCATACACCTATCCCC
280





TCCTTTTAAA
26
TCCTTTTAAAACAAAAC
281





TGATTAAGGT
27
TGATTAAGGTCGGCGCT
282





TGGTATCACA
28
TGGTATCACACAAGGGG
283





TGGTGTATGC
29
TGGTGTATGCATCGGGG
284





TGTCACTGGG
30
TGTCACTGGGCAGGCGG
285





TGTGGGAGGC
31
TGTGGGAGGCTGATGGG
286





TTTAACGGCC
32
TTTAACGGCCGCGGTAC
287





GCTCTCTATG
33
GCTCTCTATGCTGACGT
288
sign sequence receptor, delta (translocon-associated protein delta)





AGAATGAAAC
34
AGAATGAAACTGCCGGG
289
DC2 protein





AAGTGGAATA
35
AAGTGGAATAAACTGCC
290
KIAA0404 protein





GATGACGACT
36
GATGACGACTCGGGGCTT
291
symplekin; Huntingtin interacting protein I





CCCTTTCACA
37
CCCTTTCACACACACTT
292
plasmalemma vesicle associated protein





TCCTGGGGCA
38
TCCTGGGGCAGGGGCGG
293
KIAA0726 gene product





TCTATTGATG
39
TCTATTGATGTGTATGC
294
latexin protein





GGGGCTGTAT
40
GGGGCTGTATTTAAGGA
295
transforming growth factor, beta 1





CCCAGGACAC
41
CCCAGGACACCAGCTGG
296
hypothetical protein FLJ22215





GGAGCTGCTG
42
GGAGCTGCTGCTTGTGG
297
Rag C protein





TGGACAGCAG
43
TGGACAGCAGGGACCTG
298
hypothetical protein FLJ23471





TCTGGGAACA
44
TCTGGGAACAGGGACGG
299
N-myristoyltransferase 1





CCTGTGTATG
145
CCTGTGTATGTGTGTAA
300
hypothetical protein dJ1181N3.1





GGCAAGAAGA
46
GGCAAGAAGAAGATCGC
301
ribosomal protein L27





AAATGCTTGG
47
AAATGCTTGGAGGTGAA
302
secreted protein, acidic, cysteine-rich (osteonectin)





CTAAAAACCT
48
CTAAAAACCTTATGACA
303
secreted protein, acidic, cysteine-rich (osteonectin)





GAGCATTGCA
49
GAGCATTGCACCACCCG
304
secreted protein, acidic, cysteine-rich (osteonectin)





GGTGGACACG
50
GGTGGACACGGATCTGC
305
secreted protein, acidic, cysteine-rich (osteonectin)





GCTCCTGAGC
51
GCTCCTGAGCCCCGGCC
306
ESTs, Weakly similar to 165992 gene MLL protein [H.sapiens]





AAGAAGTGGA
52
AAGAAGTGGAGATTGTC
307
ESTs





TGGGAAGTGG
53
TGGGAAGTGGGCTCCTT
308
maternally expressed 3





ACTCGCTCTG
54
ACTCGCTCTGTGGAGGT
309
laminin, alpha 5





TTTCAGGGGA
55
TTTCAGGGGAGGGGGAA
310
protective protein for beta-galactosidase (galactosialidosis)





ACAACGTCCA
56
ACAACGTCCAGCTGGTG
311
Melanoma associated gene





GTCTCAGTGC
57
GTCTCAGTGCTGAGGCG
312
Melanoma associated gene





CCCCCTGCCC
58
CCCCCTGCCCCTCTGCC
313
E3 ubiquitin ligase SMURF1





AGAAACCACG
59
AGAAACCACGGAAATGG
314
collagen, type IV, alpha 1





GACCGCAGGA
60
GACCGCAGGAGGGCAGA
315
collagen, type IV, alpha 1





GTGCTACTTC
61
GTGCTACTTCTTCTTCT
316
collagen, type IV, alpha 1





GATAACTACA
62
GATAACTACATTACCTG
317
insulin-like growth factor binding protein 7





TGGCTGTGAC
63
TGGCTGTGACTGTGACT
318
gene predicted from cDNA with a complete coding sequence





GAGTGAGACC
64
GAGTGAGACCCAGGAGC
319
Thy-1 cell surface antigen





GAGTGGCTAC
65
GAGTGGCTACCCGCCGC
320
ESTs, Weakly similar to T28770 hypothetical protein W03D2.1-







Caenorhabditis elegans






GACTCAGGGA
66
GACTCAGGGATTTGTTG
321
GTP binding protein 2





GTTATATGCC
67
GTTATATGCCCGGGAGA
322

Homo sapiens mRNA; cDNA DKFZp586D0918 (from clone






GAGGCGCTGC
68
GAGGCGCTGCTGCCACC
323
cutaneous T-cell lymphoma-associated tumor antigen se20-4;






differentially expressed nucleolar TGF-beta 1 target protein






(DENTT)





GAGCTCTGAG
69
GAGCTCTGAGATCACCC
324
dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)





GCCAGCCAGT
70
GCCAGCCAGTGGCAAGC
325
Smoothelin





ATGGCAACAG
71
ATGGCAACAGATCTGGA
326
integrin, alpha 5 (fibronectin receptor, alpha polypeptide)





AAGGAGTTAC
72
AAGGAGTTACACTAGTC
327
putative translation initiation factor





TCCCACAAGG
73
TCCCACAAGGCTGCTTG
328
retinoic acid induced 14





TAAATCCCCA
74
TAAATCCCCACTGGGAC
329
matrix metalloproteinase 9 (gelatinase B, 92kD gelatinase,






92kD type IV collagenase)





CCCGCCCCCG
75
CCCGCCCCCGCCTTCCC
330
Lutheran blood group (Auberger b antigen included)





CCCGAGGCAG
76
CCCGAGGCAGAGTCGGG
331
stanniocalcin 2





CTACGTGATG
77
CTACGTGATGAAGATGG
332
nuclear factor (erythroid-derived 2)-like 2





ATGGGTTTGC
78
ATGGGTTTGCATTTTAG
333
protein tyrosine phosphatase, non-receptor type 1





GGCATTGTCT
79
GGCATTGTCTCTGTTTC
334
integrin, alpha 10





GTGCTAAGCG
80
GTGCTAAGCGGGCCCGG
335
collagen, type VI, alpha 2





ACCGTTTGCA
81
ACCGTTTGCATTCGAAA
336
chromosome 21 open reading frame 25





CAGCGCTGCA
82
CAGCGCTGCATTGACTC
337
CDC37 (cell division cycle 37, S. cerevisiae, homolog)





GAAGACACTT
83
GAAGACACTTGGTTTGA
338
ESTs





CGCTGGGCGT
84
CGCTGGGCGTCTGGGAC
339
Rho guanine nucleotide exchange factor (GEF) 7





CACCCCTGAT
85
CACCCCTGATGTTCGCC
340
creatine kinase, brain





GCCCCCCTGC
86
GCCCCCCTGCCCCGTGC
341
hypothetic protein FLJ10297





CCCCCTGCCC
87
CCCCCTGCCCTCGCCTG
342
hypothetical protein FLJ10350





AGCATAAAAA
88
AGCATAAAAATGCGTGC
343
TNF-induced protein





GGGCTGGACG
89
GGGCTGGACGGCTGCGT
344
tumor necrosis factor receptor superfamily, member 12






(translocating chain-association membrane protein)





CTGCCAACTT
90
CTGCCAACTTCTAACCG
345
cofillin 1 (non-muscle)





AAGTGGATAG
91
AAGTGGATAGATACTTC
346
splicing factor proline/glutamine rich (polypyrimidine tract-






binding protein-associated)





CGTACTGAGC
92
CGTACTGAGCGCTTTGG
347
splicing factor proline/glutamine rich (polypyrimdine tract-






binding protein-associated)





CCGCTTACTC
93
CCGCTTACTCTGTTGGG
348
v-ets avian erythroblastosis virus E26 oncogene homolog 1





GGGGCTTCTG
94
GGGGCTTCTGTAGCCCC
349
protease, cysteine, 1 (legumain)





CCCGTCCGGA
95
CCCGTCCGGAACGTCTA
350
ribosomal protein L13





AGTTCCACCA
96
AGTTCCACCAGAAAGCC
351
chromosome 22 open reading frame 5





GGCCTCCAGC
97
GGCCTCCAGCCACCCAC
352
zinc finger protein 144 (Mel-18)





GGAGGCTGAG
98
GGAGGCTGAGGTGGGAG
353
degenerative spermatocyte (homolog Drosophila; lipid desaturase)





CAGAGGCGTC
99
CAGAGGCGTCCGCAGGT
354
eukaryotic translation initiation factor 2C, 2





GACCAGCCTT
100
GACCAGCCTTCAGATGG
355
mitochondrial ribosomal protein L45





GAGGATGGTG
101
GAGGATGGTGTCCTGAG
356
prostate tumor over expressed gene 1





TCGTCGCAGA
102
TCGTCGCAGAAGGCGCT
357
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7






(14.5kD; B14.5a)





GGGGCTGCCC
103
GGGGCTGCCCAGCTGGA
358
tumor endothelial marker 1 precursor





CTGTACATAC
104
CTGTACATACTTTTTGG
359
NS1-binding protein





GCGACGAGGC
105
GCGACGAGGCGCGCTGG
360
ribosomal protein L38





GCCAAGTGAA
106
GCCAAGTGAACTGTGGC
361
tuftelin-interacting protein





AAGATAAACT
107
AAGATAAACTCTGGGCC
362
HLA class II region expressed gene KE2





GAGAGTGTAC
108
GAGAGTGTACTGGCACT
363
translocase of inner mitochondrial membrane 17 homolog A (yeast)





CCACTGCAGT
109
CCACTGCACTCCGGCCT
364
sudD (suppressor of bimD6, Aspergillus nidulans) homolog





CCACCCTCAC
110
CCACCCTCACACACACA
365
heparan sulfate proteoglycan 2 (perlecan)





CAGACCATTG
111
CAGACCATTGTTTGATC
366
SEC24 (S. cerevisiae) related gene family, member A





GGGATTTCTG
112
GGGAGCTGCGCCAACGG
367
NADH dehydrogenase (ubiquinone) Fe-S protein 7 (20kD)






(NADH-coenzyme Q reductase)





GGGATTTCTG
113
GGGATTTCTGTGTCTGC
368
DNA segment on chromosome X and Y (unique) 155 expressed sequence





CTTCCAGCTA
114
CTTCCAGCTAACAGGTC
369
annexin A2





CAGAAACAGA
115
CAGAAACAGACTGGGGG
370

Homo sapiens clone 24670 mRNA sequence






TCTGTGCTCA
116
TCTGTGCTCAGGAAGAG
371
hypothetical protein





TGCAATAGGT
117
TGCAATAGGTGAGAGAA
372
matrix metalloproteinase 10 (stromelysin 2)





ATGGCCAACT
118
ATGGCCAACTTCCACCT
373
KIAA1049 protein





TCACACAGTG
119
TCACACAGTGCCTGTCG
374
G protein-coupled receptor





GGCTTAGGAT
120
GGCTTAGGATGTGAATG
375
hypothetical protein FLJ20401





GGGAGGGGTG
121
GGGAGGGGTGGGGGTG
376
matrix metalloproteinase 14 (membrane-inserted)





GAAGTAGAAG
122
GAAGTAGAAGGTAAGGA
377
KIAA0470 gene product





CACCCTGTAC
123
CACCCTGTAGAGTTGCC
378
solute carrier family 29 (nucleoside transporters), member 1





ATGTTTACAA
124
ATGTTTACAAGATGGCG
379
stanniocalcin 1





CAAACTGGTC
125
CAAACTGGTCTAGGTCA
380
stanniocalcin 1





GTAATGACAG
126
GTAATGACAGATGCAAG
381
stanniocalcin 1





ACCTGCCGAC
127
ACCTGCCGACAGTGTTG
382
tumor suppressor deleted in oral cancer-related 1





TGATGCGCGC
128
TGATGCGCGCTTTGTTG
383
tumor suppressor deleted in oral cancer-related 1





TGGCCCCAGG
129
TGGCCCCAGGTGCCACC
384
apolipoprotein C-I





GCCTGCTGGG
130
GCCTGCTGGGCTTGGCT
385
glutathione peroxidase 4 (phospholipid hydroperoxidase)





TGCCTGTGGT
131
TGCCTGTGGTCCCAGCT
86
ESTs





GAGGGTATAC
132
GAGGGTATACTGAGGGG
387
transcription factor binding to IGHM enhancer 3





GGAGCCAGCT
133
GGAGCCAGCTGACCTGC
388
hypothetical protein DKFZp762A227





GAGCCTCAGG
134
GAGCCTCAGGTGCTCCC
389
hypothetical protein FLJ22362





TACTTCACAT
135
TACTTCACATACAGTGC
390
CD59 antigen p18-20 (antigen identified by monoclonal antibodies






16.3A5, EJ16, EJ30, EL32 and G344)





TAATCCCAGC
136
TAATCCCAGCACTTTGG
391
PRO0628 protein





CACCTTCCAG
137
CACCTTCCAGCCCGGGG
392
melanoma-associated antigen recognised by cytotoxic T lymphocytes





GAGTCTGTTC
138
GAGTCTGTTCGTGACTC
393
LOC88745





GGATTTTGGT
139
GGATTTTGGTCTCTGTC
394

Homo sapiens beta-1, 3-galactosyltransferase-6 (B3GALT6) mRNA






TGCCTGTAGT
140
TGCCTGTAGTCCTAGTT
395
sprouty (Drosophila) homolog 4





TTACAAACAG
141
TTACAAACAGAAAAGCT
396
sprouty (Drosophila) homolog 4





TCTTCTTTCA
142
TCTTCTTTCAGAATGGG
397

Homo sapiens mRNA; cDNA DKFZp434E1515 (from clone






AGCACATTTG
143
AGCACATTTGATATAGC
398
coactosin-like protein





CAGGGCTCGC
144
CAGGGCTCGCGTGCGGG
399
hypothetical protein FLJ21865





GCTGGTCCCA
145
GCTGGTCCCAGGGCCAG
400
ESTs, Weakly similar to T31613 hypothetical protein






Y50E8A.i-Caenorhabditis elegans [C.elegans]





TCCACGCCCT
146
TCCACGCCCTTCCTGGC
401
K1AA0685 gene product





TTGCAATAGC
147
TTGCAATAGCAAAACCC
402
hypothetical protein FLJ10980





AGGGCTTCCA
148
AGGGCTTCCAATGTGCT
403
ribosomal protein L10





CTGGGTTAAT
149
CTGGGTTAATAAATTGC
404
ribosomal protein S19





AACCTGGGAG
150
AACCTGGGAGGTGGAGG
405
ESTs





GGCAACGTGG
151
GGCAACGTGGTAGAGGC
406
Huntingtin iteracting protein K





GGATGCGCAG
152
GGATGCGCAGGGGAGGC
A07

Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 50374






CACCTGTAGT
153
CACCTGTAGTCCTAGCT
408
EST





GTGGTGGGCG
154
GTGGTGGGCGCCTGTAG
409
EST





GCAGGGTGGG
155
GCAGGGTGGGGAGGGG
410
v-akt murine thymoma viral oncogene homolog 2





CAAGCATCCC
156
CAAGCATCCCCGTTCCA
411
EST





TGGGGGCCGA
157
TGGGGGCCGATGGGCAG
412
transducin-like enhancer of split 2, homolog of Drosophila E(sp1)





TCAGTGTATT
158
TCAGTGTATTAAAACCC
413
KIAA1870 protein





GGCAAGCCCC
159
GGCAAGCCCCAGCGCCT
414
ribosomal protein L10a





CCTAGCTGGA
160
CCTAGCTGGATTGCAGA
415
peptidylprolyl isomerase A (cyclophilin A)





GCAAAACCGT
161
GCAAAACCCTGCTCTCC
416
ESTs, Weakly similar to ubiquitous TPR motif, Y isoform [H.sapiens]





GCTGGTTCCT
162
GCTGGTTCCTGAGTGGC
417
hypothetical protein FLJ23239





GCACCTCAGC
163
GCACCTCAGCCAGGGGT
418
hypothetical protein DKFZp761H221





ACCAGCTGTC
164
ACCAGCTGTCCAGGGGC
419
KIAA1887 protein





TTTGAATCAG
165
TTTGAATCAGTGCTAGA
420

Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 701679






AGACTAGGGG
166
AGACTAGGGGCCGGAGC
421

Homo sapiens cDNA FLJ30634 fis, clone CTONG2002453






AGCTCAGTGA
167
AGCTCAGTGAGAAGGGC
422

Homo sapiens cDNA FLJ32203 fis, clone PLACE6003038, weakly similar







to ZINC FINGER PROTEIN 84





GGCCAACATT
168
GGCCAACATTTGGTCCA
423

Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1035904






TTTGTGGGCA
169
TTTGTGGGCAGTCAGGC
424
hypothetical protein LOC57333





ATTGTAGACA
170
ATTGTAGACAATGAGGG
425
myonsin ID





CCCTAGGTTG
171
CCCTAGGTTGGGCCCCT
426
plexin B2





AAATCACCAA
172
AATACAATCAAGGC
427
lectin, galactoside-binding, soiuble, 8 (galectin 8)





GGCTGCAGTC
173
GGCTGCAGTCTTCTTCC
428
double ring-finger protein, Dorfin





GTGGCAGGCG
174
GTGGCAGGCGCCTGTAG
429
DKFZP434B168 protein





TAAAGGCACA
175
TAAAGGCACAGTGGCTC
430
LIM domain binding 2





GGCTCCTGGC
176
GGCTCCTGGCTCTGGAC
431
integrin beta 4 binding protein





ATATTAGGAA
177
ATATTAGGAAGTCGGGG
432
Synaptopodin





GCTTCAGTGG
178
GCTTCAGTGGGGGAGAG
433
ESTs





TGATTAAAAC
179
TGATTAAAACAAGTTGC
434
insulin induced gene 1





AGCCACCACG
180
AGCCACCACGCCTGGTC
435
acetyl LDL receptor; SREC





GGCGGCTGCA
181
GGCGGCTGCAGAGCCTG
436
excision repair cross-complementing rodent repair deficiency,






complementation group 1 (includes overlapping antisense sequence)





TGTTTGGGGG
182
TGTTTGGGGGCTTTTAG
437
hypothetical protein FLJ22329





CCTGCCTCGT
183
CCTGCCTCGTAGTGAAG
438
schwannomin-interactiing protein 1





AGGCCTGGGC
184
AGGCCTGGGCCTCTGCG
439
PTEN induced putative kinase 1





CAAAACTGTT
185
CAAAACTGTTTGTTGGC
440
myosin X





GAGAGGACAT
186
GAGAGGACATTGGAGGG
441

Homo sapiens cDNA FLJ32424 fis, clone SKMUS2000954, moderately







similar to Homo sapiens F-box protein Fbx25 (FBX25) 97





GAGTTAGGCA
187
GAGTTAGGCACTTCCTG
442
golgi phosphoprotein 1





CCGTAGTGCC
188
CCGTAGTGCCTTTATGG
443
splicing factor, arginine/serine-rich 6





CATAAACGGG
189
CATAAACGGGCACACCC
444
laminin, gamma 3





TCCCTGGCAG
190
TCCCTGGCAGAGGGCTT
445
cysteine-rich protein 2





GAGGCCATCC
191
GAGGCCATCCCCAACCC
446
U6 snRNA-associated Sm-like protein LSm7





TTGCCTGGGA
192
TTGCCTGGGATGCTGGT
447
hypothetical protein FLJ10707





CTGTCAGCGG
193
CTGTCAGCGGCTGCCCC
448

Homo sapiens, Similar to RIKEN cDNA 2310012N15 gene, clone







IMAGE:3342825, mRNA, partial cds





AACGCGGCCA
194
AACGCGGCCAATGTGGG
449
macrophage migration inhibitory factor (glycosylation-inhibiting






factor)





GGTTTGGCTT
195
GGTTTGGCTTAGGCTGG
450
ubiqtanol-cytochrome c reductase hinge protein





GATTTTTGTG
196
GATTTTTGTGGTGTGGG
451
gap junction protein, alpha 1, 43kd (connexin 43)





GGCTGCCCTG
197
GGCTGCCCTGGGCAGCC
452
dihydropyrimidinase-like 3





ATGGCAACAG
198
ATGGAAAGAAACCAA
453
aquaporin 1 (channel-forming integral protein, 28kD)





CGCTGTGGGG
199
CGCTGTGGGGTGCAGAC
454
protein expressed in thyroid





GGCAGCCAGA
200
GGCAGCCAGAGCTCCAA
455
macrophage myristoylated alanine-rich C kinase substrate





AGAGCAAACC
201
AGAGCAAACCGTAGTCC
456
procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine






hydroxylase, Ehlers-Danlos syndrome type VI)





TTTCCCTCAA
202
TTTCCCTCAAAGACTCT
457
protease, serine, 11 (IGF binding)





TCCCCGTGGC
203
TCCCCGTGGCTGTGGGG
458
24-dehydrocholesterol reductase





TTCTCCCAAA
204
TTCTCCCAAATACCGTT
459
collagen, type IV, alpha 2





GGCTGGGGGC
205
GGCTGGGGGCCAGGGCT
460
profilin 1





CCCTACCCTG
206
CCCTACCCTGTTACCTT
461
apolipoprotein D





TAGGACCCTG
207
TAGGACCCTGCAGGGGG
462
hyaluronoglucosaminidase 2





GTTTTTGCTT
208
GTTTTTGCTTCAGCGGC
463
hypothetical protein FLJ22678





CTTGATTCCC
209
CTTGATTCCCACGCTAC
464
quiescin Q6





GCTTGGCTCC
210
GCTTGGCTCCCAAAGGG
465
ras homolog gene family, member A





GGTGGCACTC
211
GGTGGCATCAGTCTCT
466
ras homolog gene family, member A





ACCTGTGACC
212
ACCTGTGACCAGCACTG
467
plasminogen activator, urokinase





ACTGAGGAAA
213
ACTGAGGAAAGGAGCTC
468
insulin-like growth factor binding protein 3





TGCAGCGCCT
214
TGCAGCGCCTGCGGCCT
469
uridine phosphorylase





CTGGGGGGAA
215
CTGGGGGGAAGGGACTG
470
KIAA0638 protein





GTGCTATTCT
216
GTGCTATTCTGGGGCTG
471
B7 homolog 3





GGAGGGGGCT
217
GGAGGGGGCTTGAAGCC
472
lamin A/C





GTGCCTGAGA
218
GTGCCTGAGAGGCAGGC
473
lamin A/C





TCACAGGGTC
219
TCACAGGGTCCCCGGGG
474
lamin A/C





GGGCTCCCTG
220
GGGCTCCCTGGCCCTGG
475
regulator of G-protein signalling 12





GCCCCAGGTA
221
GCCCCAGGTAGGGGGAC
476
proteasome (prosome, macropain) 26S subunit, non-ATPase, 8





GAAAGTGGCT
222
GAAAGTGGCTGTCCTGG
477

Homo sapiens, Similar to RIKEN cDNA 5730528L13 gene, clone







MGC:17337 IMAGE:4213591, mRNA, complete cds





TCCCTGGCTG
223
TCCCTGGCTGTTGAGGC
478
prosaposin (variant Gaucher disease and variant metachromatic





ACAGAGCACA
224
ACAGAGCACAGCTGCCC
479
laminin, alpha 4





CTTTGCACTC
225
CTTTGCACTCTCCTTTG
480
transcription elongation factor A (SII), 1





ATGCTCCCTG
226
ATGCTCCTGAGGAGCT
481
lectin, galactoside-binding, soluble, 3 binding protein





CCGTCCAAGG
227
CCGTCCAAGGGTCCGCT
482
ribosomal protein S16





GGGCCCCCTG
228
GGGCCCCCTGGGCAGTG
483
glycophorin C (Gerbich blood group)





CTTATGCTGC
229
CTTATGCTGCTGGTGCC
484
endothelin receptor type B





GGTTATTTTG
230
GGTTATTTTGGAGTGTA
485
serine (or cysteine) proteinase inhibor, dade E (nexin,






plasminogen activator inhibitor type 1), member 1





GCCTGTCCCT
231
GCCTGTCCCTCCAAGAC
486
Biglycan





AAGATGAGGG
232
AAGATGAGGGGGCAGGC
487
small nuclear ribonucleoprotein polypeptide B″





CCAACAAGAA
233
CCAACAAGAATGCATTG
488
transmembrane 4 superfamily member 2





AAGGATGCGG
234
AAGGATGCGGTGATGGC
489
TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated






factor, 28 kD





TGTCATCACA
235
TGTCATCACAGACACTT
490
lysyl oxidase-like 2





CAGGCTTTTT
236
CAGGCTTTTTGGCTTCC
491
SRY (sex determining region Y)-box 4





TCAAGTTCAC
237
TCAAGTTCACTGCCTGT
492
SOX4 SRY (sex determining region Y)-box 4





TCCCTGGGCA
238
TCCCTGGGCAGCTTGAG
493
SRY (sex determining region Y)-box 4





CAGGAGTTCA
239
CAGGAGTTCAAAGAAGG
494
actin, related protein 2/3 complex, subunit 2 (34 kD)





CAGGTGGTTC
240
CAGGTGGTTCTGCCATC
495

Homo sapiens cDNA: FLJ23507 fis, clone LNG03128






GCCCACATCC
241
GCCCACATCCGCTGAGG
496
hypothetical protein FLJ12442





GCTGGGGTGG
242
GCTGGGGTGGGGGTGG
497
Fas (TNFRSF6)-associated via death domain





GACCTCCTGC
243
GACCTCCTGCCCTGGGG
498
mitogen-activated protein kinase kinase kinase 11





AGTGAATAAA
244
AGTGAATAAATGTCTTG
499
TEK tyrosine kinase, endothelial (venous malformations, multiple






cutaneous and mucosal)





AAGGTTCTTC
245
AAGGTTCTTCTCAAGGG
500
insulin receptor





AGCCTGGACT
246
AGCCTGGACTGAGCCAC
501
cell membrane glycoprotein, 110000M(r) (surface antigen)





CAACCCAGAT
247
CAACCCAGATTGGGGTG
502

Homo sapiens cDNA FLJ11863 fis, clone HEMBA1006926






TGCTTCTGCC
248
TGCTTCTGCCACCCTGC
503
jagged 1 (Alagille syndrome)





CAGGTGACAA
249
CAGGTGACAAGGGCCCT
504
KIAA0304 gene product





GGCCGGGGGC
250
GGCCGGGGGCAGTTCTC
505
pre-B-cell leukemia transcription factor 2





GTGCGCTAGG
251
GTGCGCTAGGGCCCCGG
506

Homo sapiens cDNA FLJ31238 fis, clone KIDNE2004864






AGGCTGTCCA
252
AGGCTGTCCAGGGTCTG
507
p53-induced protein





TGTTATGTCC
253
TGTTATGTCCATTTTGC
508
complement component 1, q subcomponent, receptor 1





TTTCCCAAAC
254
TTTCCCAAACTGTGAGG
509
complement component 1, q subcomponent, receptor 1





GGGGATGGGG
255
GGGGATGGGGTACTGCC
510

Homo sapiens, clone IMAGE:3908182, mRNA, partial cds






















TABLE 2





SEQ ID NO:
Unigene ID
OMIMID
gene symbol
locuslink id
Cellular Component




















33
Hs.102135
300090
SS
6748
endoplasmic reticulum, membrane


34
Hs.103180


35
Hs.105850

KIAA0404
23130


36
Hs.107019
602388
SPK
8189
cytoplasm, nucleoplasm


37
Hs.107125



membrane


38
Hs.107809

KIAA0726
9746
membrane


39
Hs.109276


40
Hs.1103
190180
TGFB1
7040


41
Hs.110443


42
Hs.110950


43
Hs.110964


44
Hs.111039
160993
NMT1
4836


45
Hs.11114

DJ1181N3
58476


46
Hs.111611

RPL27
6155
intracellular, ribosome


47
Hs.111779
182120
SPARC
6678
basement membrane


48
Hs.111779
182120
SPARC
6678
basement membrane


49
Hs.111779
182120
SPARC
6678
basement membrane


50
Hs.111779
182120
SPARC
6678
basement membrane


51
Hs.111988


52
Hs.112238


53
Hs.112844


54
Hs.11669
601033
LAMA5
3911
basement lamina


55
Hs.118126
256540
PPGB
5476
endoplasmic reticulum, lysosome


56
Hs.118893
600134
D2S448
7837
cellular_component unknown


57
Hs.118893
600134
D2S448
7837
cellular_component unknown


58
Hs.119120
605568
SMURF1
57154
intracellular


59
Hs.119129
120130
COL4A1
1282
collagen


60
Hs.119129
120130
COL4A1
1282
collagen


61
Hs.119129
120130
COL4A1
1282
collagen


62
Hs.119206
602867
IGFBP7
3490
extracellular


63
Hs.124


64
Hs.125359
188230
THY1
7070
integral plasma membrane protein


65
Hs.127824


66
Hs.13011

GTPBP2
54676


67
Hs.13350


68
Hs.136164


69
Hs.143897
603009
DYSF
8291
plasma membrane


70
Hs.149098
602127
SMTN
6525
actin cytoskeleton


71
Hs.149609
135620
ITGA5
3678
cytoskeleton, extracellular matrix,


72
Hs.150580

SUI1
10209
cellular_component unknown


73
Hs.15165


74
Hs.151738
120361
MMP9
4318
extracellular matrix, extracellular space


75
Hs.155048
111200
LU
4059
integral plasma membrane protein,


76
Hs.155223
603665
STC2
8614


77
Hs.155396
600492
NFE2L2
4780
nucleus


78
Hs.155894
176885
PTPN1
5770
cytoplasm, soluble fraction


79
Hs.158237
604042
ITGA10
8515
cytoskeleton, extracellular matrix,


80
Hs.159263
120240
COL6A2
1292
extracellular matrix


81
Hs.16007


82
Hs.160958
605065
CDC37
11140


83
Hs.16450


84
Hs.172813
605477
P85SPR
8874


85
Hs.173724
123280
CKB
1152
cytoplasm


86
Hs.173739


87
Hs.177596


88
Hs.17839

GG2
25816


89
Hs.180338
603366
TNFRSF12
8718
integral plasma membrane protein,


90
Hs.180370
661442
CFL1
1072
cytoskeleton, nucleus


91
Hs.180610
605199
SFPQ
6421
nucleus


92
Hs.180610
605199
SFPQ
6421
nucleus


93
Hs.18063
164720
ETS1
2113
nucleus


94
Hs.18069
602620
PRSC1
5641


95
Hs.180842
113703
RPL13
6137
cytosolic ribosome, intracellular


96
Hs.182626


97
Hs.184669
600346
ZNF144
7703
nucleus


98
Hs.185973

DEGS
8560
endoplasmic reticulum, integral plasma


99
Hs.193053
606229
EIF2C2
27161
cellular_component unknown


100
Hs.19347

MRPL45
84311
mitochondrion


101
Hs.19555


102
Hs.19561
602139
NDUFA7
4701
membrane fraction, mitochondrion,


103
Hs.195727
606064
TEM1
57124
extracellular matrix


104
Hs.197298

NS1
10625
spliceosome, transcription factor


105
Hs.2017
604182
RPL38
6169
60S ribosomal subunit, intracellular,


106
Hs.20225


107
Hs.205736
605660
HKE2
10471
prefoldin


108
Hs.20716
605057
TIM17
10440
integral plasma membrane protein,


109
Hs.209061
603579
SUDD
8780


110
Hs.211573
142461
HSPG2
3339
basement membrane, extracellular


111
Hs.211612

SEC24A
10802
COPII vesicle coat, endoplasmic


112
Hs.211914
601825
NDUFS7
4727
mitochondrion, NADH dehydrogenase


113
Hs.21595
312095
DXYS155E
8227
cellular_component unknown


114
Hs.217493
151740
ANXA2
302
plasma membrane, soluble fraction


115
Hs.21906


116
Hs.22129


117
Hs.2258
185260
MMP10
4319
extracellular matrix, extracellular space


118
Hs.227835


119
Hs.23016

RDC1
57007
integral membrane protein, membrane


120
Hs.233955


121
Hs.2399
600754
MMP14
4323
extracellular matrix, integral plasma


122
Hs.25132


123
Hs.25450
602193
SLC29A1
2030
integral plasma membrane protein,


124
Hs.25590
601185
STC1
6781


125
Hs.25590
601185
STC1
6781


126
Hs.25590
601185
STC1
6781


127
Hs.25664

DOC
10263


128
Hs.25664

DOC
10263


129
Hs.268571
107710
APOC1
341


130
Hs.2706
138322
GPX4
2879
mitochondrion


131
Hs.272106


132
Hs.274184
314310
TFE3
7030
nucleus


133
Hs.274453


134
Hs.27836


135
Hs.278573
107271
CD59
966
membrane fraction, plasma membrane


136
Hs.278941


137
Hs.279869
604853
MAAT1
10573


138
Hs.283636


139
Hs.284284


140
Hs.285814


141
Hs.285814


142
Hs.287830


143
Hs.289092

CLP
23406
intracellular


144
Hs.29288


145
Hs.296234


146
Hs.296406


147
Hs.29716


148
Hs.29797
312173
RPL10
6134
60S ribosomal subunit, intracellular,


149
Hs.298262
603474
RPS19
6223
40S ribosomal subunit, intracellular,







ribosome


150
Hs.299257


151
Hs.300954


152
Hs.302741


153
Hs.311780


154
Hs.312191


155
Hs.326445
164731
AKT2
208


156
Hs.327884


157
Hs.332173
601041
TLE2
7089
nucleus


158
Hs.334604

KIAA1870
85301
collagen


159
Hs.334895

RPL10A
4736
60S ribosomal subunit, intracellular,


160
Hs.342389
123840
PPIA
5478
cytoplasm


161
Hs.344224


162
Hs.34516


163
Hs.347297


164
Hs.348428


165
Hs.348967


166
Hs.350065


167
Hs.351706


168
Hs.36353


169
Hs.39619

LOC57333
57333


170
Hs.39871
606539
MYO1D
4642
myosin


171
Hs.3989
604293
PLXNB2
23654
membrane


172
Hs.4082
606099
LGALS8
3964
extracellular space


173
Hs.48320

DORFIN
25897
centrosome


174
Hs.48604


175
Hs.4980
603450
LDB2
9079
nucleus


176
Hs.5215
602912
ITGB4BP
3692
extrinsic plasma membrane protein,


177
Hs.5307


178
Hs.54828


179
Hs.56205
602055
INSIG1
3638


180
Hs.57735

SREC
8578
membrane


181
Hs.59544
126380
ERCC1
2067
nucleus


182
Hs.61478


183
Hs.61490


184
Hs.6163

PINK1
65018


185
Hs.61638


186
Hs.61661


187
Hs.6831


188
Hs.6891
601944
SFRS6
6431
nucleus


189
Hs.69954
604349
LAMC3
10319
extracellular matrix, membrane


190
Hs.70327
601183
CRIP2
1397


191
Hs.70830

LOC51690
51690
nucleus, small nucleolar


192
Hs.7187


193
Hs.7247


194
Hs.73798
153620
MIF
4282
extracellular space


195
Hs.73818

UQCRH
7388
mitochondrial electron transport chain


196
Hs.74471
121014
GJA1
2697
connexon, integral plasma membrane


197
Hs.74566
601168
DPYSL3
1809


198
Hs.74602
107776
AQP1
358
integral plasma membrane protein,


199
Hs.7486


200
Hs.75061

MLP
65108


201
Hs.75093
153454
PLOD
5351
endoplasmic reticulum


202
Hs.75111
602194
PRSS11
5654
extracellular space


203
Hs.75616


204
Hs.75617
120090
COL4A2
1284
collagen, collagen type IV


205
Hs.75721
176610
PFN1
5216
actin cytoskeleton


206
Hs.75736
107740
APOD
347
extracellular space


207
Hs.76873
603551
HYAL2
8692
lysosome


208
Hs.7718


209
Hs.77266
603120
QSCN6
5768


210
Hs.77273
165390
ARHA
387
cytoskeleton


211
Hs.77273
165390
ARHA
387
cytoskeleton


212
Hs.77274
191840
PLAU
5328
extracellular space


213
Hs.77326
146732
IGFBP3
3486
extracellular space


214
Hs.77573
191730
UP
7378


215
Hs.77864


216
Hs.77873
605715
B7
80381
cellular_component unknown


217
Hs.77886
150330
LMNA
4000
lamin, nuclear lamina, nucleus


218
Hs.77886
150330
LMNA
4000
lamin, nuclear lamina, nucleus


219
Hs.77886
150330
LMNA
4000
lamin, nuclear lamina, nucleus


220
Hs.78281
602512
RGS12
6002
extrinsic plasma membrane protein,


221
Hs.78466

PSMD8
5714
19S proteasome regulatory particle


222
Hs.78531


223
Hs.78575
176801
PSAP
5660
extracellular space, integral membrane


224
Hs.78672
600133
LAMA4
3910
basement lamina


225
Hs.78869
601425
TCEA1
6917
nucleus


226
Hs.79339
600626
LGALS3BP
3959
extracellular space, membrane


227
Hs.80617
603675
RPS16
6217
40S ribosomal subunit, intracellular,


228
Hs.81994
110750
GYPC
2995
integral plasma membrane protein,


229
Hs.82002
131244
EDNRB
1910
integral plasma membrane protein,


230
Hs.82085
173360
SERPINE1
5054


231
Hs.821
301870
BGN
633
extracellular matrix


232
Hs.82575
603520
SNRPB2
6629
nucleus, snRNP U2e


233
Hs.82749
300096
TM4SF2
7102
integral plasma membrane protein,


234
Hs.83126
600772
TAF2I
6882
nucleus, TFIID complex


235
Hs.83354

LOXL2
4017
extracellular space, membrane


236
Hs.83484
184430
SOX4
6659
nucleus


237
Hs.83484


238
Hs.83484
184430
SOX4
6659
nucleus


239
Hs.83583
604224
ARPC2
10109
actin cytoskeleton, Arp2/3 protein


240
Hs.84063


241
Hs.84753


242
Hs.86131
602457
FADD
8772
cytoplasm


243
Hs.89449
600050
MAP3K11
4296


244
Hs.89640
600221
TEK
7010
integral plasma membrane protein,


245
Hs.89695
147670
INSR
3643
integral plasma membrane protein,


246
Hs.90107

GP110
11047
integral plasma membrane protein,


247
Hs.9096


248
Hs.91143
601920
JAG1
182
membrane


249
Hs.92236

KIAA0304
9757
nucleus


250
Hs.93728
176311
PBX2
5089
nucleus


251
Hs.9408


252
Hs.96908

PIG11
9537


253
Hs.97199
120577
C1QR
22918
integral plasma membrane protein,


254
Hs.97199
120577
C1QR
22918
integral plasma membrane protein,


255
Hs.99093









Isolated and purified nucleic acids, according to the present invention are those which are not linked to those genes to which they are linked in the human genome. Moreover, they are not present in a mixture such as a library containing a multitude of distinct sequences from distinct genes. They may be, however, linked to other genes such as vector sequences or sequences of other genes to which they are not naturally adjacent. Tags disclosed herein, because of the way that they were made, represent sequences which are 3′ of the 3′ most restriction enzyme recognition site for the tagging enzyme used to generate the SAGE tags. In this case, the tags are 3′ of the most 3′ most NlaIII site in the cDNA molecules corresponding to mRNA. Nucleic acids corresponding to tags may be RNA, cDNA, or genomic DNA, for example. Such corresponding nucleic acids can be determined by comparison to sequence databases to determine sequence identities. Sequence comparisons can be done using any available technique, such as BLAST, available from the National Library of Medicine, National Center for Biotechnology Information. Tags can also be used as hybridization probes to libraries of genomic or cDNA to identify the genes from which they derive. Thus, using sequence comparisons or cloning, or combinations of these methods, one skilled in the art can obtain full-length nucleic acid sequences. Genes corresponding to tags will contain the sequence of the tag at the 3′ end of the coding sequence or of the 3′ untranslated region (UTR), 3′ of the 3′ most recognition site in the cDNA for the restriction endonuclease which was used to make the tags. The nucleic acids may represent either the sense or the anti-sense strand. Nucleic acids and proteins although disclosed herein with sequence particularity, may be derived from a single individual. Allelic variants which occur in the population of humans are included within the scope of such nucleic acids and proteins. Those of skill in the art are well able to identify allelic variants as being the same gene or protein. Given a nucleic acid, one of ordinary skill in the art can readily determine an open reading frame present, and consequently the sequence of a polypeptide encoded by the open reading frame and, using techniques well known in the art, express such protein in a suitable host. Proteins comprising such polypeptides can be the naturally occurring proteins, fusion proteins comprising exogenous sequences from other genes from humans or other species, epitope tagged polypeptides, etc. Isolated and purified proteins are not in a cell, and are separated from the normal cellular constituents, such as nucleic acids, lipids, etc. Typically the protein is purified to such an extent that it comprises the predominant species of protein in the composition, such as greater than 50, 60 70, 80, 90, or even 95% of the proteins present.


Using the proteins according to the invention, one of ordinary skill in the art can readily generate antibodies which specifically bind to the proteins. Such antibodies can be monoclonal or polyclonal. They can be chimeric, humanized, or totally human. Any functional fragment or derivative of an antibody can be used including Fab, Fab′, Fab2, Fab′2, and single chain variable regions. So long as the fragment or derivative retains specificity of binding for the endothelial marker protein it can be used. Antibodies can be tested for specificity of binding by comparing binding to appropriate antigen to binding to irrelevant antigen or antigen mixture under a given set of conditions. If the antibody binds to the appropriate antigen at least 2, 5, 7, and preferably 10 times more than to irrelevant antigen or antigen mixture then it is considered to be specific.


Techniques for making such partially to fully human antibodies are known in the art and any such techniques can be used. According to one particularly preferred embodiment, fully human antibody sequences are made in a transgenic mouse which has been engineered to express human heavy and light chain antibody genes. Multiple strains of such transgenic mice have been made which can produce different classes of antibodies. B cells from transgenic mice which are producing a desirable antibody can be fused to make hybridoma cell lines for continuous production of the desired antibody. See for example, Nina D. Russel, Jose R. F. Corvalan, Michael L. Gallo, C. Geoffrey Davis, Liise-Anne Pirofski. Production of Protective Human Antipneumococcal Antibodies by Transgenic Mice with Human Immunoglobulin Loci Infection and Immunity April 2000, p. 1820-1826; Michael L. Gallo, Vladimir E. Ivanov, Aya Jakobovits, and C. Geoffrey Davis. The human immunoglobulin loci introduced into mice: V (D) and J gene segment usage similar to that of adult humans European Journal of Immunology 30: 534-540, 2000; Larry L. Green. Antibody engineering via genetic engineering of the mouse: XenoMouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies Journal of Immunological Methods 231 11-23, 1999; Yang X-D, Corvalan J R F, Wang P, Roy CM-N and Davis C G. Fully Human Anti-interleukin-8 Monoclonal Antibodies: Potential Therapeutics for the Treatment of Inflammatory Disease States. Journal of Leukocyte Biology Vol. 66, pp 401-410 (1999); Yang X-D, Jia X-C, Corvalan J R F, Wang P, C G Davis and Jakobovits A. Eradication of Established Tumors by a Fully Human Monoclonal Antibody to the Epidermal Growth Factor Receptor without Concomitant Chemotherapy. Cancer Research Vol. 59, Number 6, pp 1236-1243 (1999); Jakobovits A. Production and selection of antigen-specific fully human monoclonal antibodies from mice engineered with human Ig loci. Advanced Drug Delivery Reviews Vol. 31, pp: 33-42 (1998); Green L and Jakobovits A. Regulation of B cell development by variable gene complexity in mice reconstituted with human immunoglobulin yeast artificial chromosomes. J. Exp. Med. Vol. 188, Number 3, pp: 483-495 (1998); Jakobovits A. The long-awaited magic bullets: therapeutic human monoclonal antibodies from transgenic mice. Exp. Opin. Invest. Drugs Vol. 7(4), pp: 607-614 (1998); Tsuda H, Maynard-Currie K, Reid L, Yoshida T, Edamura K, Maeda N, Smithies O, Jakobovits A. Inactivation of Mouse HPRT locus by a 203-bp retrotransposon insertion and a 55-kb gene-targeted deletion: establishment of new HPRT-Deficient mouse embryonic sGEM cell lines. Genomics Vol. 42, pp: 413-421 (1997); Sherman-Gold, R. Monoclonal Antibodies: The Evolution from '80s Magic Bullets To Mature, Mainstream Applications as Clinical Therapeutics. Genetic Engineering News Vol. 17, Number 14 (August 1997); Mendez M, Green L, Corvalan J, Jia X-C, Maynard-Currie C, Yang X-d, Gallo M, Louie D, Lee D, Erickson K, Luna J, Roy C, Abderrahim H, Kirschenbaum F, Noguchi M, Smith D, Fukushima A, Hales J, Finer M, Davis C, Zsebo K, Jakobovits A. Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice. Nature Genetics Vol. 15, pp: 146-156 (1997); Jakobovits A. Mice engineered with human immunoglobulin YACs: A new technology for production of fully human antibodies for autoimmunity therapy. Weir's Handbook of Experimental Immunology, The Integrated Immune System Vol. IV, pp: 194.1-194.7 (1996); Jakobovits A. Production of fully human antibodies by transgenic mice. Current Opinion in Biotechnology Vol. 6, No. 5, pp: 561-566 (1995); Mendez M, Abderrahim H, Noguchi M, David N, Hardy M, Green L, Tsuda H, Yoast S, Maynard-Currie C, Garza D, Gemmill R, Jakobovits A, Klapholz S. Analysis of the structural integrity of YACs comprising human immunoglobulin genes in yeast and in embryonic sGEM cells. Genomics Vol. 26, pp: 294-307 (1995); Jakobovits A. YAC Vectors: Humanizing the mouse genome. Current Biology Vol. 4, No. 8, pp: 761-763 (1994); Arbones M, Ord D, Ley K, Ratech H, Maynard-Curry K, Otten G, Capon D, Tedder T. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity Vol. 1, No. 4, pp: 247-260 (1994); Green L, Hardy M, Maynard-Curry K, Tsuda H, Louie D, Mendez M, Abderrahim H, Noguchi M, Smith D, Zeng Y, et. al. Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs. Nature Genetics Vol. 7, No. 1, pp: 13-21 (1994); Jakobovits A, Moore A, Green L, Vergara G, Maynard-Curry K, Austin H, Klapholz S. Germ-line transmission and expression of a human-derived yeast artificial chromosome. Nature Vol. 362, No. 6417, pp: 255-258 (1993); Jakobovits A, Vergara G, Kennedy J, Hales J, McGuinness R, Casentini-Borocz D, Brenner D, Otten G. Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy-chain joining region blocks B-cell development and antibody production. Proceedings of the National Academy of Sciences USA Vol. 90, No. 6, pp: 2551-2555 (1993); Kucherlapati et al., U.S. Pat. No. 6,1075,181.


Antibodies can also be made using phage display techniques. Such techniques can be used to isolate an initial antibody or to generate variants with altered specificity or avidity characteristics. Single chain Fv can also be used as is convenient. They can be made from vaccinated transgenic mice, if desired. Antibodies can be produced in cell culture, in phage, or in various animals, including but not limited to cows, rabbits, goats, mice, rats, hamsters, guinea pigs, sheep, dogs, cats, monkeys, chimpanzees, apes.


Antibodies can be labeled with a detectable moiety such as a radioactive atom, a chromophore, a fluorophore, or the like. Such labeled antibodies can be used for diagnostic techniques, either in vivo, or in an isolated test sample. Antibodies can also be conjugated, for example, to a pharmaceutical agent, such as chemotherapeutic drug or a toxin. They can be linked to a cytokine, to a ligand, to another antibody. Suitable agents for coupling to antibodies to achieve an anti-tumor effect include cytokines, such as interleukin 2 (IL-2) and Tumor Necrosis Factor (TNF); photosensitizers, for use in photodynamic therapy, including aluminum (III) phthalocyanine tetrasulfonate, hematoporphyrin, and phthalocyanine; radionuclides, such as iodine-131 (131I), yttrium-90 (90Y), bismuth-212 (212Bi), bismuth-213 (213Bi), technetium-99m (99mTc), rhenium-186 (186Re), and rhenium-188 (188Re); antibiotics, such as doxorubicin, adriamycin, daunorubicin, methotrexate, daunomycin, neocarzinostatin, and carboplatin; bacterial, plant, and other toxins, such as diphtheria toxin, pseudomonas exotoxin A, staphylococcal enterotoxin A, abrin-A toxin, ricin A (deglycosylated ricin A and native ricin A), TGF-alpha toxin, cytotoxin from chinese cobra (naja naja atra), and gelonin (a plant toxin); ribosome inactivating proteins from plants, bacteria and fungi, such as restrictocin (a ribosome inactivating protein produced by Aspergillus restrictus), saporin (a ribosome inactivating protein from Saponaria officinalis), and RNase; tyrosine kinase inhibitors; ly207702 (a difluorinated purine nucleoside); liposomes containing antitumor agents (e.g., antisense oligonucleotides, plasmids which encode for toxins, methotrexate, etc.); and other antibodies or antibody fragments, such as F(ab).


Those of skill in the art will readily understand and be able to make such antibody derivatives, as they are well known in the art. The antibodies may be cytotoxic on their own, or they may be used to deliver cytotoxic agents to particular locations in the body. The antibodies can be administered to individuals in need thereof as a form of passive immunization.


Characterization of extracellular regions for the cell surface and secreted proteins from the protein sequence is based on the prediction of signal sequence, transmembrane domains and functional domains. Antibodies are preferably specifically immunoreactive with membrane associated proteins, particularly to extracellular domains of such proteins or to secreted proteins. Such targets are readily accessible to antibodies, which typically do not have access to the interior of cells or nuclei. However, in some applications, antibodies directed to intracellular proteins may be useful as well. Moreover, for diagnostic purposes, an intracellular protein may be an equally good target since cell lysates may be used rather than a whole cell assay.


Computer programs can be used to identify extracellular domains of proteins whose sequences are known. Such programs include SMART software (Schultz et al., Proc. Natl. Acad. Sci. USA 95: 5857-5864, 1998) and Pfam software (BaGEMan et al., Nucleic acids Res. 28: 263-266, 2000) as well as PSORTII. Typically such programs identify transmembrane domains; the extracellular domains are identified as immediately adjacent to the transmembrane domains. Prediction of extracellular regions and the signal cleavage sites are only approximate. It may have a margin of error + or −5 residues. Signal sequence can be predicted using three different methods (Nielsen et al, Protein Engineering 10:1-6, 1997, Jagla et. al, Bioinformatics 16: 245-250, 2000, Nakai, K. and Horton, P. Trends in Biochem. Sci. 24:34-35, 1999) for greater accuracy. Similarly transmembrane (TM) domains can be identified by multiple prediction methods. (Pasquier, et. al, Protein Eng. 12:381-385, 1999, Sonnhammer et al., In Proc. of Sixth Int. Conf. on Intelligent Systems for Molecular Biology, p. 175-182, Ed J. Glasgow, T. Littlejohn, F. Major, R. Lathrop, D. Sankoff, and C. Sensen Menlo Park, Calif.: AAAI Press, 1998, Klein, et. al, Biochim. Biophys. Acta, 815:468, 1985, Nakai and Kanehisa Genomics, 14: 897-911, 1992). In ambiguous cases, locations of functional domains in well characterized proteins are used as a guide to assign a cellular localization.


Putative functions or functional domains of novel proteins can be inferred from homologous regions in the database identified by BLAST searches (Altschul et. al. Nucleic Acid Res. 25: 3389-3402, 1997) and/or from a conserved domain database such as Pfam (BaGEMan et.al, Nucleic Acids Res. 27:260-262 1999) BLOCKS (Henikoff, et. al, Nucl. Acids Res. 28:228-230, 2000) and SMART (Ponting, et. al, Nucleic Acid Res. 27, 229-232, 1999). Extracellular domains include regions adjacent to a transmembrane domain in a single transmembrane domain protein (out-in or type I class). For multiple transmembrane domains proteins, the extracellular domain also includes those regions between two adjacent transmembrane domains (in-out and out-in). For type II transmembrane domain proteins, for which the N-terminal region is cytoplasmic, regions following the transmembrane domain is generally extracellular. Secreted proteins on the other hand do not have a transmembrane domain and hence the whole protein is considered as extracellular.


Membrane associated proteins can be engineered to delete the transmembrane domains, thus leaving the extracellular portions which can bind to ligands. Such soluble forms of transmembrane receptor proteins can be used to compete with natural forms for binding to ligand. Thus such soluble forms act as inhibitors. and can be used therapeutically as anti-angiogenic agents, as diagnostic tools for the quantification of natural ligands, and in assays for the identification of small molecules which modulate or mimic the activity of a GEM:ligand complex.


Alternatively, the endothelial markers themselves can be used as vaccines to raise an immune response in the vaccinated animal or human. For such uses, a protein, or immunogenic fragment of such protein, corresponding to the intracellular, extracellular or secreted GEM of interest is administered to a subject. The immogenic agent may be provided as a purified preparation or in an appropriately expressing cell. The administration may be direct, by the delivery of the immunogenic agent to the subject, or indirect, through the delivery of a nucleic acid encoding the immunogenic agent under conditions resulting in the expression of the immunogenic agent of interest in the subject. The GEM of interest may be delivered in an expressing cell, such as a purified population of glioma endothelial cells or a populations of fused glioma endothelial and dendritic cells. Nucleic acids encoding the GEM of interest may be delivered in a viral or non-viral delivery vector or vehicle. Non-human sequences encoding the human GEM of interest or other mammalian homolog can be used to induce the desired immunologic response in a human subject. For several of the GEMs of the present invention, mouse, rat or other ortholog sequences are described herein or can be obtained from the literature or using techniques well within the skill of the art.


Endothelial cells can be identified using the markers which are disclosed herein as being endothelial cell specific. These include the human markers identified by SEQ ID NOS: 1-510. Antibodies specific for such markers can be used to identify such cells, by contacting the antibodies with a population of cells containing some endothelial cells. The presence of cross-reactive material with the antibodies identifies particular cells as endothelial. Similarly, lysates of cells can be tested for the presence of cross-reactive material. Any known format or technique for detecting cross-reactive material can be used including, immunoblots, radioimmunoassay, ELISA, immunoprecipitation, and immunohistochemistry. In addition, nucleic acid probes for these markers can also be used to identify endothelial cells. Any hybridization technique known in the art including Northern blotting, RT-PCR, microarray hybridization, and in situ hybridization can be used.


One can identify glioma endothelial cells for diagnostic purposes, testing cells suspected of containing one or more GEMs. One can test both tissues and bodily fluids of a subject. For example, one can test a patient's blood for evidence of intracellular and membrane associated GEMs, as well as for secreted GEMs. Intracellular and/or membrane associated GEMs may be present in bodily fluids as the result of high levels of expression of these factors and/or through lysis of cells expressing the GEMs.


Populations of various types of endothelial cells can also be made using the antibodies to endothelial markers of the invention. The antibodies can be used to purify cell populations according to any technique known in the art, including but not limited to fluorescence activated cell sorting. Such techniques permit the isolation of populations which are at least 50, 60, 70, 80, 90, 92, 94, 95, 96, 97, 98, and even 99% the type of endothelial cell desired, whether normal, tumor, or pan-endothelial. Antibodies can be used to both positively select and negatively select such populations. Preferably at least 1, 5, 10, 15, 20, or 25 of the appropriate markers are expressed by the endothelial cell population.


Populations of endothelial cells made as described herein, can be used for screening drugs to identify those suitable for inhibiting the growth of tumors by virtue of inhibiting the growth of the tumor vasculature.


Populations of endothelial cells made as described herein, can be used for screening candidate drugs to identify those suitable for modulating angiogenesis, such as for inhibiting the growth of tumors by virtue of inhibiting the growth of endothelial cells, such as inhibiting the growth of the tumor or other undesired vasculature, or alternatively, to promote the growth of endothelial cells and thus stimulate the growth of new or additional large vessel or microvasculature.


Inhibiting the growth of endothelial cells means either regression of vasculature which is already present, or the slowing or the absence of the development of new vascularization in a treated system as compared with a control system. By stimulating the growth of endothelial cells, one can influence development of new (neovascularization) or additional vasculature development (revascularization). A variety of model screening systems are available in which to test the angiogenic and/or anti-angiogenic properties of a given candidate drug. Typical tests involve assays measuring the endothelial cell response, such as proliferation, migration, differentiation and/or intracellular interaction of a given candidate drug. By such tests, one can study the signals and effects of the test stimuli. Some common screens involve measurement of the inhibition of heparanase, endothelial tube formation on Matrigel, scratch induced motility of endothelial cells, platelet-derived growth factor driven proliferation of vascular smooth muscle cells, and the rat aortic ring assay (which provides an advantage of capillary formation rather than just one cell type).


Drugs can be screened for the ability to mimic or modulate, inhibit or stimulate, growth of tumor endothelium cells and/or normal endothelial cells. Drugs can be screened for the ability to inhibit tumor endothelium growth but not normal endothelium growth or survival. Similarly, human cell populations, such as normal endothelium populations or glioma endothelial cell populations, can be contacted with test substances and the expression of glioma endothelial markers and/or normal endothelial markers determined. Test substances which decrease the expression of glioma endothelial markers (GEMs) are candidates for inhibiting angiogenesis and the growth of tumors. In cases where the activity of a GEM is known, agents can be screened for their ability to decrease or increase the activity.


For those glioma endothelial markers identified as containing transmembrane regions, it is desirable to identify drug candidates capable of binding to the GEM receptors found at the cell surface. For some applications, the identification of drug candidates capable of blocking the GEM receptor from its native ligand will be desired. For some applications, the identification of a drug candidate capable of binding to the GEM receptor may be used as a means to deliver a therapeutic or diagnostic agent. For other applications, the identification of drug candidates capable of mimicking the activity of the native ligand will be desired. Thus, by manipulating the binding of a transmembrane GEM receptor:ligand complex, one may be able to promote or inhibit further development of endothelial cells and hence, vascularization.


For those glioma endothelial markers identified as being secreted proteins, it is desirable to identify drug candidates capable of binding to the secreted GEM protein. For some applications, the identification of drug candidates capable of interfering with the binding of the secreted GEM it is native receptor. For other applications, the identification of drug candidates capable of mimicking the activity of the native receptor will be desired. Thus, by manipulating the binding of the secreted GEM:receptor complex, one may be able to promote or inhibit further development of endothelial cells, and hence, vascularization.


Expression can be monitored according to any convenient method. Protein or mRNA can be monitored. Any technique known in the art for monitoring specific genes' expression can be used, including but not limited to ELISAs, SAGE, microarray hybridization, Western blots. Changes in expression of a single marker may be used as a criterion for significant effect as a potential pro-angiogenic, anti-angiogenic or anti-tumor agent. However, it also may be desirable to screen for test substances which are able to modulate the expression of at least 5, 10, 15, or 20 of the relevant markers, such as the tumor or normal endothelial markers. Inhibition of GEM protein activity can also be used as a drug screen. Human and mouse GEMS can be used for this purpose.


Test substances for screening can come from any source. They can be libraries of natural products, combinatorial chemical libraries, biological products made by recombinant libraries, etc. The source of the test substances is not critical to the invention. The present invention provides means for screening compounds and compositions which may previously have been overlooked in other screening schemes. Nucleic acids and the corresponding encoded proteins of the markers of the present invention can be used therapeutically in a variety of modes. GEMs can be used to stimulate the growth of vasculature, such as for wound healing or to circumvent a blocked vessel. The nucleic acids and encoded proteins can be administered by any means known in the art. Such methods include, using liposomes, nanospheres, viral vectors, non-viral vectors comprising polycations, etc. Suitable viral vectors include adenovirus, retroviruses, and sindbis virus. Administration modes can be any known in the art, including parenteral, intravenous, intramuscular, intraperitoneal, topical, intranasal, intrarectal, intrabronchial, etc.


Specific biological antagonists of GEMs can also be used to therapeutic benefit. For example, antibodies, T cells specific for a GEM, antisense to a GEM, and ribozymes specific for a GEM can be used to restrict, inhibit, reduce, and/or diminish tumor or other abnormal or undesirable vasculature growth. Such antagonists can be administered as is known in the art for these classes of antagonists generally. Anti-angiogenic drugs and agents can be used to inhibit tumor growth, as well as to treat diabetic retinopathy, rheumatoid arthritis, psoriasis, polycystic kidney disease (PKD), and other diseases requiring angiogenesis for their pathologies.


Mouse counterparts to human GEMS can be used in mouse cancer models or in cell lines or in vitro to evaluate potential anti-angiogenic or anti-tumor compounds or therapies. Their expression can be monitored as an indication of effect. Mouse GEMs can be used as antigens for raising antibodies which can be tested in mouse tumor models. Mouse GEMs with transmembrane domains are particularly preferred for this purpose. Mouse GEMs can also be used as vaccines to raise an immunological response in a human to the human ortholog.


The above disclosure generally describes the present invention. All references disclosed herein are expressly incorporated by reference. A more complete understanding can be obtained by reference to the following specific examples which are provided herein for purposes of illustration only, and are not intended to limit the scope of the invention.


Example 1

In this study we employ SAGE transcript profiling to derive the transcriptomes from normal and neoplastic brain tissue. Moreover, we have employed a new version of SAGE, long SAGE, allowing for the derivation of 21 by SAGE tags. These longer tags allow for the direct interrogation of genomic DNA, identifying unique locations of cell-specific transcription. Endothelial cells from normal brain and different stages of gliomas were expression profiled and compared to each other and to the colon endothelial cell data. Distinct sets of genes define global tumor and normal endothelial cell markers as well as defining glioma-specific endothelial markers. This expanded tumor endothelial cell database will likely provide further insights into the complex regulatory mechanisms governing tumor angiogenesis.


Example 2

Tissue procurement and endothelial cell isolation. Five separate brain tissue samples (Table 1) were resected and immediately subjected to endothelial cell isolation with slight modifications to the protocol described previously. St Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K. E., Montgomery, E., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., and Kinzler, K. W. (2000). Genes expressed in human tumor endothelium. Science 289, 1197-202.


Briefly, samples were surgically excised and submerged in DMEM. The samples were minced into 2 centimeter cubes and subjected to tissue digestion with a collagenase cocktail. Samples were mixed at 37° C. until dissolved. Cells were spun down and washed two times with PBS/BSA and filtered through successive nylon mesh filters of 250, 100 and 40 microns. Samples were resuspended in PBS/BSA and applied to a 30% Percoll gradient centrifuging for 15 minutes at 800 g. 5 ml off the top of the percoll gradient was diluted in 50 ml DMEM and cells pelleted, washed with PBS and resuspended in 3 ml PBS/BSA. Cells were filtered through falcon blue top filter tubes, spun down and resuspended in 1 ml PBS/BSA. 100 microliters of prewashed ant-CD45 magnetic beads (Dynal) were added and the solution allowed to gently mix for ten minutes. Bead-bound cells were discarded and the supernatant transferred to a fresh microcentrifuge tube. 10 microliters of P1H12 mAB (1:100) (Brain N1, T1, and T2 samples) or UEA-I lectin (Brain N2 and T3 samples) was added and the samples were mixed gently at 4° C. for 45 minutes. Cells were pelleted and washed 3 times in PBS/BSA and resuspended in 500 microliters PBS/BSA. Prewashed goat anti-mouse M450 dynabeads were added to each tube and allowed to mix for 15 minutes at 4° C. Bead-bound cells were washed 8 times with PBS/BSA and resuspended in a final volume of 500 microliters PBS. Cells were counted and frozen at −70° C. prior to RNA extraction.


Example 3

RNA isolation and SAGE library generation. RNA was isolated from the selected cells and initially subjected to RT-PCR analysis to determine the relative abundance of specific, known endothelial cell markers. The microSAGE protocol St Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K. E., Montgomery, E., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., and Kinzler, K. W. (2000). Genes expressed in human tumor endothelium. Science 289, 1197-202 (server www, domain name sagenet.org, directory sage protocol) was used to generate high-quality longSAGE libraries employing the tagging enzyme MmeI instead of BsmFI. 21 base tags were defined by capillary sequencing using a combination of an ABI 3700 and ABI 3100. The sample descriptions and sequencing depth are shown in Table 3.


Example 4

Data analysis. Long SAGE tags derived from the brain endothelial samples were reduced to short tags to allow for the integration of colon endothelial SAGE data. Aggregate short tags were derived from the long tags. Any short tag counts that had more than one corresponding long tag representative were summed and the counts represented as one short tag. Both sequencing errors and legitimate long tag derivatives contribute to the generation of multiple long tags. For transcript and genome mapping, differential long tags were employed. Differential gene expression was evaluated as follows: For the two normal brain samples, either the maximum or minimum value was used for determining tumor/normal and normal/tumor ratios, respectively. For the three brain tumor samples, the median value was used for the tumor/normal whereas the maximum value was used for the normal/tumor ratios. A two parameter family of beta distributions was used to assess the probability of observing two fold differences in the observed SAGE tag abundances. Chen, H., Centola, M., Altschul, S. F., and Metzger, H. (1998). Characterization of gene expression in resting and activated mast cells. J Exp Med 188, 1657-68.


Example 5

The following provides a detailed protocol useful for isolating brain endothelial cells. All steps were done at 4° C. in cold room and in centrifuge except digestion.

  • 1) Take sample from operating room and submerge in known volume of DMEM+ in 50 ml conical tube to measure tumor volume by displacement. Cut off 2 small pieces of tumor on dry ice and store at ±70° C. for mRNA extraction/immunohistochemistry/in situ analysis.
  • 2) Take sample from conical and place in small amount of DMEM+in 10 cm Tissue Culture dish in hood. Mince specimen into 2 mm cubes with sterile scalpel.
  • 3) Transfer minced specimen to small autoclaved erlenmeyer flask and add 5× volume of digestion cocktail. Sample volumes >5 ml should be split into multiple flasks.
  • 4) Mix in bacterial shaker or in 37° C. room on rotating shaker for 45 minutes or until sample is dissolved. Titrate with 10 ml piper every 15 minutes. Once a good cell suspension is obtained, remove and transfer to 50 ml conical.


Remainder of protocol done at 4° C.

  • 5) Spin down at 1500 RPM (600×g) at 4° C. for 5 minutes.
  • 6) Wash 2× with PBS/BSA and spin down again. Pool samples.
  • 7) Filter through Nylon Mesh (250, 100, 40 micron).
  • 8) Spin down.
  • 9) Resuspend n PBS/BSA at ½ the original tumor volume.
  • 10) Apply sample in 500 ul aliquots to preformed 30% Percoll gradient (Gradients needed=volume of original sample).
  • 11) Spin at 1750 RPM (800 g) for 15 minutes.
  • 12) Remove top 5 ml Percoll from each tube and dilute with DMEM to 50 ml volume.
  • 13) Pellet cells in centrifuge at 1500 RPM. Pool pelleted cells.
  • 14) Wash 2× with PBS/BSA and resuspend in 3 ml PBS/BSA.
  • 15) Filter through Falcon Blue Top Filter tube.
  • 16) Spin down and resuspend in 1 ml PBS/BSA in a 1.5 ml microcentrigufe tube.
  • 17) Add 100 μl of prewashed anti-CD45 beads (hematopoietic depletion) to solution and rotate end over end in cold room for ten minutes. [For brain tissue isolation, an additional negative selection with BerEP4 epithelial depletion is not needed]
  • 18) Remove bead-bound cells and transfer supernatant to a fresh microcentrifuge tube. Save bead-bound sample by freezing at ±70° C. Repeat extraction to ensure complete removal of all beads.
  • 19) Add 10 ul of P1H12 mAb (1:100) to cells and mix in cold room with end-over-end rotation for 45 minutes. [As an alternative, selection using UEA1 lectin also provides quality endothelial cell selection.]
  • 20) Pellet cells and wash 3× with PBS/BSA.
  • 21) Resuspend cells in 500 ul of PBS/BSA.
  • 22) Divide sample into four 1.5 ml microcentrifuge tubes (125 ul per tube) and bring volume up to 800 ul. Add 50 ul of prewashed goat anti-mouse M450 dynabeads to each tube.
  • 23) Rotate tubes in cold room for 15 minutes.
  • 24) Separate with magnet and save supernatant as staining control, tumor/brain fraction.
  • 25) Rinse 8× with PBS/BSA.
  • 26) Pool beads into single microcentrifuge tube.
  • 27) Resuspend final cells in 500 ul plain PBS.
  • 28) Take 5 ul of solution and combine with 5 ul of Magic DAPI and count on hemacytometer.
  • 29) Remove 10 k cells for staining for quality control based on hemacytometer results
  • 30) Separate beads again and freeze remainder at −70° C. for mRNA extraction.


Example 6

This example describes the preparation of SAGE tags from mRNA extracted from brain endothelial cells. The preparation is described with reference to standard SAGE tag preparation procedures as are known in the art.

    • All of the template was used in the PCR SAGE ditag step. Usually we take only a small portion of our template, dilute it and perform ˜300 PCR reactions. For these libraries we used all of our material, diluted it and performed ˜1200 PCR reactions.
      • During the post-amplified PCR product purification step we normally do a standard large volume phenol/chloroform extraction and remove the aqueous layer which contains the product of interest. For these libraries we used Eppendorfs Phase Lock product which creates a physical barrier between the aqueous and organic layers thereby decreasing the amount of product you leave behind. This product was used for all P/C extractions in the second half of the protocol.
      • Digesting the amplified PCR products with NlaIII to release the ditag of interest is usually done in one reaction. For these libraries I divided the material into thirds and performed 3 NlaIII reactions in the hopes of yielding more released ditag.
      • Due to the low amount of material, upon entering the concatemer and digested pZERO ligation reaction, I modified the recipe for this reaction to accommodate this. Standard reaction calls for 6 ul of concatemers, 2 ul of 5× ligase buffer, 1 ul digested pZERO vector, and 1 ul of high concentrate ligase. I modified it to 6 ul of concatemers, 2 ul of 5× ligase buffer, 0.3-0.5 ul of digested pZERO vector, 1 ul high concentrate ligase and filled the missing volume with water. My intention was to favor the concatemer to pZERO ligation reaction relative to the competing pZERO to pZERO ligation reaction.
    • Most gels during the procedure showed weak amounts of product for visualization and the concatemer gels showed no visible product via the naked eye (we cut out certain fractions regardless).


Example 7

Microarray Analysis. Custom 50 nucleotide oligomer arrays were constructed containing 606 unique gene elements. The 606 genes were derived from tumor and normal induced genes from both colon and brain data (328 genes), as well as 278 genes from both literature reviews and housekeeping genes. Arrays were interrogated with Cy3 and Cy5 dye-swapped labelled aRNA samples comparing HMVECs grown on plastic, collagen, fibrin, or Matrigel.


Example 8

In situ Hybridizations and Immunohistochemistry. In situ hybridizations for PV I, VEGFR2 and vWF were carried out as described previously (10). Co-staining of PV1 and CD31 was carried out as follows: Four 500 nucleotide riboprobe fragments specific for PV1 were transcribed and used to probe formalin fixed 5 micron tissue sections. Final detection of the bound riboprobes were delayed until after the CD31 IHC staining. After PV1 hybridization and washing, tissue sections were fixed for 20 minutes in 4% formaldehyde. After a brief rinse in TBS, antigen retrieval was carried out using DAKO target retrieval solution (DAKO, Cat#S1699) according to manufacturer's instructions. After a five minute wash in TBS, slides were digested with Proteinase K at 20 ng/ml in TBS for 20 minutes at 37T, then blocked for 20 minutes at room temperature in block (10% Goat serum/0.5% Casein/0.05% Tween-20/PBS). Slides were incubated with DAKO CD31 (Cat#M0823) at a final concentration of 1 microgram/slide in block solution, for 60 minutes at room temperature. After two 5 minute TBST (DAKO, Cat#S3306) washes at room temperature, PV1 riboprobe and CD31 antibody were detected with Streptavidin-Cy2 (Jackson ImmunoResearch, Cat#016-220-084) at 5 micrograms/slide for the PV1 riboprobe, and goat anti-mouse-Cy3 (Jackson ImmunoResearch, Cat# 115-165-146) at 2.5 micrograms/slide for CD3 1, for 60 minutes at room temperature. After three Ywashes in TBST, the slides were mounted with antifade medium containing DAPI nuclear counter-stain, cover-slipped and stored at −20′C until viewing. Single images of DAPI, Cy2 and Cy3 images were acquired separately on a Zeiss Axioplan at 40× with a Hammamatsu camera, then merged together to form a composite image using universal imaging metamorph software, and stored at −20C until viewing.


Example 9

Capillary-like tubule formation assay. The formation of capillary-like tubular structures was assessed in Matrigel-coated multiwell plates essentially as described previously (12). Briefly, 300 microliters of Matrigel (BD, Bedford, Mass.) was added to each well of a 24 well plate and allowed to polymerize at 37′C for 30 minutes. HMVECs (BioWhittaker) were infected with adenovius harboring Tem.1 or GFP gene or empty vector (EV) for 67 hours at 300 MOI (Multiplicity Of Infection). Cells were then seeded at a density of 30×103 cells/well in 500 microliters EGM-2 medium with supplements (BioWhittaker) in Matrigel-coated plates and incubated at 37′C for 24 hours and viewed using a Nikon Eclipse TE200 microscope under a phase contrast and photographed. Images were analyzed using software Scion Image (Scion Corporation, Frederick, Md.) under the mode of integrated density.


Example 9

Cell Proliferation Assay. HMVEC proliferation was assessed by the Cell Titer-Glo Luminescent Cell Viability Assay (Promega, Madison, Wis.) in 96-well cell culture plates. HMVECs were seeded at 2,000 cells per well in 100 microliters medium and plates were incubated at 37′C for 48 hours. Reagent was added to each well according to manufacture's instruction, and fluorescence was measured using the Millipore CytoFluor2350.


Example 10

Five independent endothelial cell populations were purified from glioma tumor tissue and normal brain tissue. In this study, the tissue defined as normal is derived from patients with epilepsy who have undergone a temporal lobectomy. The samples are summarized in Table 3. Samples N1, T1 and T2 were ultimately P1H12-selected and samples N2 and T3 were UEA-I selected. Prior to SAGE analysis, each sample was assessed for the relative mRNA abundance for vWF, Glial fibrillary acidic protein (GFAP) and EF1 by RT-PCR. Abundant levels of vWF and the control housekeeper EF1, and low levels of the glial cell-specific gene GFAP suggested the cell population was primarily endothelial (data not shown). SAGE analysis was performed to a depth of approximately 50,000 tags (Table 3). For data analysis, each SAGE project was normalized to exactly 50,000 tags. Pairwise comparisons between expression data derived from tumor samples selected with P1H12 or UEA-I showed correlation coefficients around 80%, slightly higher than a comparison between two tumor samples both selected with P1H12. This suggests that selecting endothelial cells with either P1H12 or UEA-I results in highly similar cell populations. Moreover, nearly half of the tumor specific markers revealed in this study are induced 4 fold in each of the normal samples used, suggesting the normal samples are similar populations as well. With this in mind, we felt that combining data for the two normal samples and for the three tumor samples was appropriate.









TABLE 3







Samples used in this study.












Tags



Sample
Description
Generated
EC Selection





Brain N1
Normal temporal lobectomy ECs
43,000
P1H12


Brain N2
Normal temporal lobectomy ECs
49,000
UEA-I


Brain T1
Grade IV Glioma Ecs
46,000
P1H12


Brain T2
Grade III Glioma Ecs
50,000
P1H12


Brain T3
Grade IV Glioma Ecs
58,000
UEA-I


Colon N*
Normal colon Ecs
96,000
P1H12


Colon T*
Tumor colon Ecs
96,000
P1H12


Fetal Brain
Normal bulk
204,000 



Fetal Kidney
Normal bulk
 50,000+











Genes specific for endothelial cells showed expression levels consistent with the previously examined colon endothelial SAGE data (Table 4). Additionally, markers specific for epithelial, hematopoeitic or glial cells showed limited or no expression in the brain endothelial libraries suggesting little contamination from non-endothelial cell populations (Table 4). Finally, the data generated here allow for the derivation of alt gene EC prediction class of which 6 have been previously described as EC-specific (Huminiecki, L., and Bicknell, R. (2000). In silico cloning of novel endothelial-specific genes. Genome Res 10, 1796-806.) (data not shown). This provides further evidence of pure EC populations used for this study.









TABLE 4







Cell specificity markers.















Gene
Specificity
Colon N
Colon T
Brain N1
Brain N2
Brain T1
Brain T2
Brain T3


















Hevin
EC
161
69
51
99
223
121
48


VWF
EC
35
33
12
53
37
51
110


Tie2/Tek
EC
4
2
2
4
1
4
3


CD34
EC
5
2
3
10
12
4
11


CD14
Hematopoeitic
1
1
1
2
0
0
1


CK8
Epithelial
1
2
0
0
2
1
1


GLUT1
Brain EC
0
1
8
37
2
25
8


GFAP
Glial
0
0
0
0
0
0
0









Genes expressed preferentially in glioma derived endothelial cells as opposed to normal endothelial cells are potentially involved in regulating angiogenesis-dependent tumor growth. Specific parameters for the sorting of SAGE data and the layering of additional statistical filters allowed for a conservative estimate of legitimate differentially expressed genes (see Methods). Excluding mitochondrial genes, 131 genes were observed to be induced in the glioma endothelial cells based on a four fold induction ratio. Only 14 genes can be entertained as glioma-specific when additional statistical filters are applied (Table 5). In this case, a two fold parameter family of distributions was used to establish a 90% probability of observing at least a 2 fold difference in values. Only one of these twelve genes, apolipoprotein D, shows higher expression in the stage La glioma than at least one of the stage IV tumors. This suggests that many of the highly induced glioma endothelial genes revealed in this analysis may be involved in later stages of angiogenesis where the initiation of vascular sprouting has already occurred or are glioma type specific showing representation in the astrocytoma and not oligodendroglioma-derived ECs. Less highly induced genes, or genes primarily induced in the less aggressive tumor stage, may be more reflective of angiogenesis initiation. Several genes regulating extracellular matrix architecture are revealed as highly induced in this study. HSPG2 (perlecan), several type IV collagen transcript variants, and matrix metalloprotease 14 (MMP14) have all been shown to play a role in remodeling the extracelullar matrix. Interestingly, other genes that play roles in either cellular signaling or cell-cell communication are also highly expressed exclusively in glioma-associated endothelial cells. Melanoma associated antigen (MG50), endothelin receptor, the G-protein coupled receptor RDC-1, and integrin αV are all cell surface proteins previously demonstrated to play a role in signaling cascades. Although the endothelin receptor, RDC-1 and integrin αV have previously been shown to regulate angiogenesis, MG50 does not have an association with angiogenesis. Moreover, MG50 was previously shown to be selectively associated with several types of tumor cells with a function yet to be defined. It is noteworthy that the p53-induced, brain-specific angiogenesis inhibitor (BAI-1) was expressed to significant levels but restricted to the earlier stage tumor present in this study (data not shown). It is possible that the loss of expression of BAI-1 in the later tumor stages reflects the need to more aggressively advance vascular development. Other than the detection of a differential HEYL SAGE tag, no other colon endothelial markers were observed to be preferentially expressed in the grade III tumor. In total, of the 14 tumor induced genes listed, 12 are either present on the cell surface or secreted. The localization of the remaining two gene products has yet to be determined as these genes remain uncharacterized. Finally, it is noteworthy that only a select few genes show significant (>2 tags) expression in a fetal brain library where angiogenesis is expected to be robust.


In contrast to the highly biased localization of glioma-induced endothelial cell gene expression defined above, genes that are induced in the normal endothelial cells relative to glioma endothelial cells show a radically different cellular distribution. Twenty-one genes are induced 4 fold or greater in the normal endothelial cells. Filtering for genes with a 50% or greater chance of having greater than 2 fold difference in transcript abundance reduces this list to 14 genes (Table 6). Protein products predicted for these 14 genes show a range of cellular localizations with 4 gene products being intracellular, 5 being integral membrane proteins, 3 extracellular, and one each either secreted, on the cell surface or a nuclear membrane receptor. Several of these genes have functions consistent with either tumor suppressor or anti-angiogenic functions. These anti-proliferative functions have been ascribed to the early growth response gene 1 (EGR1), BTG2, Fruppel-like factor 4 (KLF4), and the serine protease inhibitor SPINT2 although associations with angiogenesis are limited to SPINT2. The down-regulation of these genes in each of the three glioma tumors suggests that these genes may function to encode proteins with anti-angiogenic properties. Both SPINT2 and BTG2 are secreted and may act via paracrine mechanisms. Also noteworthy is the preferential expression of the secreted protein MT1A as this metalothionein may serve as an antioxidant potentially attenuating DNA damage within adjacent cells. Interestingly, EGR1 and KLF4′ encode transcription factors suggesting that some part of the anti-angiogenic pathway revealed here may be initiated by these gene products. With the exception of MT1A, none of the above genes show differential expression in colon tumor ECs and may therefore be glioma-specific EC markers.


The specificity of gene expression for tumor EC subtypes is important to define and can be addressed with the glioma EC data integrated with data obtained previously for colon EC populations. A limited number of genes are preferentially expressed in both brain and colon normal EC populations. In contrast, 16 genes were induced at least 4 fold in both colon and brain tumor EC fractions. 12 of these genes also met the criteria of having a greater than 50% chance of being at least 2 fold differential (Table 7). The majority of these genes (7) are collagen transcripts. However, tumor endothalial marker 1 (TEM1), THY1, and RDC-1 also show consistent induction in the different tumor EC cells. This limited conservation of tumor-induced EC expression suggests highly specific EC expression profiles dependent on the tissue source. TEM1 expression has been validated on tissue arrays harboring tissue slices from astrocytomas (data not shown).


Defining the specificity of gene expression to particular cell types can assist in determining function and designing therapeutics. Our non-endothelial cell SAGE database currently contains 76 libraries encoding 255,000 unique SAGE transcripts. The epithelial cell lines derive from lung, ovary, kidney, prostate, breast, colon, pancreas. Additional non-epithelial sources include cardiomyocytes, melanocytes, glioblastoma and monocytes. Genes which show induction in glioma ECs and demonstrate a restricted expression in non-EC cells may be ideal targets for anti-angiogenic therapies. Allowing for 1 or fewer tags in any non-EC library and at least a four-fold induction in glioma ECs yielded only 5 genes (Table 8). Some of these genes are likely not EC-specific due to the relatively limited number of cell types included within the non-EC database. However, both PV-1 and Plexin A2 (PLXNA2) are interesting genes with potential functional relevance to angiogenesis regulation.


The SAGE tag that defines PLXNA2 falls outside of the current mRNA boundaries residing 3′ of the ultimate exon. RT-PCR results, however, have confirmed transcription of mRNA containing this tag in the tumor samples used to derive the SAGE data. Plexins share homology with the scatter factor/hepatocyte growth factor (SF/HGF) family of receptors encoded by the MET gene family [Tamagnone, L., Artigiani, S., Chen, H., He, Z., Ming, G. I., Song, H., Chedotal, A., Winberg, M. L., Goodman, C. S., Poo, M., Tessier-Lavigne, M., and Comoglio, P. M. (1999). Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99, 71-80.] Earlier results have demonstrated a link between SF/HGF expression and increase tumorigencity [Bowers, D. C., Fan, S., Walter, K. A., Abounader, R., Williams, J. A., Rosen, E. M., and Laterra, J. (2000). Scatter factor/hepatocyte growth factor protects against cytotoxic death in human glioblastoma via phosphatidylinositol 3-kinase- and AKT-dependent pathways. Cancer Res 60, 4277-83.] Moreover, SF/HGF promotes this increased tumorigencity with concordant stimulation in angiogenesis [Lamszus, K., Laterra, J., Westphal, M., and Rosen, E. M. (1999). Scatter factor/hepatocyte growth factor (SF/HGF) content and function in human gliomas. Int J Dev Neurosci 17, 517-30.] In vivo targeting of SF/HGF was demonstrated to inhibit glioma growth and angiogenesis [Abounader, R., Lal, B., Luddy, C., Koe, G., Davidson, B., Rosen, E. M., and Laterra, J. (2002). In vivo targeting of SF/HGF and c-met expression via U1snRNA/ribozymes inhibits glioma growth and angiogenesis and promotes apoptosis. Faseb J 16, 108-10.]. Plexins are known to function as coreceptors with neuropilin 1 functioning as a receptor for semaphorin and, in turn, regulating neuronal guidance and cell association [Tamagnone, 1999, supra]. As neuropilin-1 and Plexin association can serve to receive signals from semaphorins to guide neuronal growth, it is conceivable that a Plexin-neuropilin association may regulate angiogenic growth in a manner analogous to KDR-neuropilin complexes signaling VEGF responses. Plexin A2 shows very low level expression in colon ECs and is not differentially induced in colon tumor ECs. It is noteoworthy that another plexin, plexin B2 (PLXNB2), also showed a five fold increase in glioma EC expression but did not make the statistical threshold demanded for Table 8. Plexin B2 was previously shown to be differentially induced in brain tumors [Shinoura, N., Shamraj, O. I., Hugenholz, H., Zhu, J. G., McBlack, P., Warnick, R., Tew, J. J., Wani, M. A., and Menon, A. G. (1995). Identification and partial sequence of a cDNA that is differentially expressed in human brain tumors. Cancer Lett 89, 215-21.] The upregulation of plexins in glioma ECs allows for a hypothesis whereby SF/HGF directly stimulates EC migration and proliferation. The novel discovery of a consistently upregulated level of Plexin A2 in gliomas requires further evidence for a functional link between tumor levels of plexin A2 and angiogenesis regulation, particularly in the brain.


PV-1 (also called PLVAP for plasmallema vesicle associated protein), is a recently discovered type II integral membrane glycoprotein shown to colocalize with caveolin-1. Stan, R. V., Arden, K. C., and Palade, G. E. (2001). cDNA and protein sequence, genomic organization, and analysis of cis regulatory elements of mouse and human PLVAP genes. Genomics 72, 304-13. Interestingly, this protein was the first to be shown to localize to the stomatal diaphragms and transendothelial channels within caveolae. The specific function of PV-1 remains unknown. PV-1 is expressed at substantial levels in colon ECs but is not expressed differentially between normal and tumor colon ECs. The upregulation of this caveolae-associated protein in gliomas may provide a means for specifically targeting glioma-associated endothelial cells as well as potentially providing a therapeutic delivery mechanism to the underlying tumorigenic cells (Marx, J. (2001). Caveolae: a once-elusive structure gets some respect. Science 294, 1862-5.))


From this study there is also the potential to define brain EC specific genes irrespective of function or differential expression in normal or tumor tissue. Applying the same criteria as that applied for defining EC restricted glioma induced genes, only two genes, TNFα-induced protein 3 and JUNB, show consistent expression in the brain EC samples but severely limited expression in non-EC databases.


The blood brain barrier within brain capillary endothelial cells results in a restricted diffusion of both small and large molecules as compared to non-brain EC junction complexes. As a result of this, brain capillary ECs facilitate molecular exchange via a tightly regulated, or catalyzed transport system. Any differential expression of catalyzed membrane transporters between normal and tumor tissue may provide a means to selectively deliver therapies to tumor cells. The insulin receptor (IR) has been known for some time to be a marker for brain capillary ECs and to facilitate delivery of drugs. One of the most highly induced, glioma-specific genes in this study is the IR (Table 8). The high induction of IR transcripts in gliomas was not previously recognized and may provide a selective delivery mechanism to cancer cells as these receptors are also proposed to reside within caveolae structures [Smith, R. M., Jarret, L. (1988). Lab. Invest. 58, 613-629.] Overall, very few transporters showed a differential induction in glioma-associated ECs as compared to their normal counterpart (Table 9). This is counter to previous suggestions linking altered expression of transporters with histologic grade of CNS tumors [Guerin, C., Wolff, J. E., Laterra, J., Drewes, L. R., Brem, H., and Goldstein, G. W. (1992). Vascular differentiation and glucose transporter expression in rat gliomas: effects of steroids. Ann Neurol 31, 481-7.] Only one other gene, SLC1A5 Solute carrier family 1 member 5 (neutral amino acid transporter), showed a greater than 4 fold induction in glioma-derived ECs. It should be stated, however, that the standard SAGE tag for integrin αV is shared with aquaporin. Long tag derivations of these two genes revealed that both integrin αV and aquaporin are induced in glioma ECs. Aquaporin may play a role in caveolae swelling that accompanies VEGF stimulated EC growth [Roberts, W. G., and Palade, G. E. (1997). Neovasculature induced by vascular endothelial growth factor is fenestrated. Cancer Res 57, 765-72.] Only one membrane transporter, Na+/K+ transporting ATP1A2 ATPase, was reciprocally repressed in glioma-derived ECs. It remains possible that certain transporters were missed in this analysis due to incorrect functional assignment. Nonetheless, the low number of differentially regulated transport facilitators suggests a small number of these genes need to be transcriptionally activated to accommodate any necessary increase in protein abundance required for tumor growth.


Table 10 shows genes induced in glioma endothelial cells but not in colon tumor or breast tumor endothelial cells.


Table 11 shows genes which encode transporters which are repressed in glioma endothelial cells.


Table 12 shows genes which encode proteins which are localized to the nucleus of both brain and colon tumor endothelial cells.


Table 13 shows genes which encode proteins which are localized to the cytoplasm of both brain and colon tumor endothelial cells.


Table 14 shows genes which encode proteins which are extracellular from both brain and colon tumor endothelial cells.


Table 15 shows genes which encode proteins which are localized to the membrane of both brain and colon tumor endothelial cells.


Table 16 shows genes which encode proteins which are induced in both brain and colon tumor endothelial cells.


Table 17 shows additional tumor endothelial markers in brain.


Table 18 shows tumor endothelial markers in the brain which are cytoplasmic.


Table 19 shows tumor endothelial markers in the brain which are nuclear.


Table 20 shows tumor endothelial markers in the brain which are membrane associated.


Table 21 shows tumor endothelial markers in the brain which are extracellular.


Table 22 shows tumor endothelial markers in the brain which are unsorted with respect to cellular localization.


REFERENCES



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TABLE 5





T/N
T/N prob.
SAGE Tag
UG ID
UG description
localization





















17
95
GTCTCAGTGC
116893
Melanoma associated gene MG50
surface/secreted






14
90
CTTATGCTGC
82002
endothelin receptor type B
surface





13
99
CCACCCTCAC
211573
HSPG2 Perlecan
extracellular





13
94
GTGCTACTTC
119129
collagen, type IV, alpha 1
extracellular





12
98
GAGTGAGACC
345843
Thy-1 cell surface anbgen
surface





10
94
ATGGCAACAG
149609
ITGA5 integrin alpha 5 (Fn receptor) receptor
surface





9
91
TCACACAGTG
23016
G protein-coupled receptor RDC-1
surface





8
100
GACCGCAGG
119129
collagen, type IV, alpha 1
extracellular





8
97
GGGAGGGGTG
239
matrix metalloproteinase 14 (membrane-inserted)
extracellular





7
99
CCCTACCCTG
75736
apolipoprotein D
extracellular





8
97
TTCTCCCAAA
75617
collagen, type IV, alpha 2
extracellular





6
98
GGATGCGCAG
302741

Homo sapiens mRNA full length insert cDNA clone EU






5
98
GTGCTAAGCG
159263
collagen, type VI, alpha 2 Exon 1
extracellular





4
93
CCCAGGACAC
110443

Homo sapiens cDNA: FLJ22215 fis, clone HRC01580.























TABLE 6





Brain
Brain







N/T
N/T prob
SAGE Tag
UG ID
UG description
Localization





















9
72
TAGTTGGAAA
1119
nuclear receptor subfamily 4, group A, member 1 NR4A1
nuclear








membrane





9
72
AAGGGCGCGG
1378
annexin A3 ANXA3
membrane





9
72
AGCTGTGCCA
348254
metallothionein 1A (functional) MT1A
extracellular





7
60
ACAAAATCAA
110613
nuclear pore complex interacting protein SMG-1
membrane





6
68
GCCTGCAGTC
31439
serine prolease inhibitor, Kunitz type, 2 SPINT2
extracellutar





6
52
ACCAGGTCCA
5167
solute carrier family 5 (sodium-dependent vitamin
membrane





334549





6
52
GGCTAATTAT
34114
ATPase. Na+/K+ transporting. alpha 2 (+) polypepti
membrane





6
75
TTTAAATAGC
7934
KLF4 Kruppel-like factor 4 (gut)
intracellular





5
81
CAGTTCATTA
326035
early growth response 1 EGR1
intracellular





5
61
CTGCCGTGAC
75462
BTG family, member 2 BTG2
extracellular





5
65
TTTTAACTTA
160483
erythrocyle membrane protein band 7.2 (stomatin)
membrane





4
77
TAGAAACCGG
8997
heat shock 70kD protein 1A HSP70
intracellular





4
77
CTTCTTGCC
272572
hemoglobin, alpha 2
intracellular





347939





4
53
TAGAAAAAAT
8906
syntaxin 7
surface






















TABLE 7





Brain
colon







T/N
T/N
SAGE Tag
UG ID
UG description
localization





















13
4
GTGCTAGTTC
119129
collagen, type IV, alpha 1
extracellular






12
16
GAGTGAGACC
125359
Thy-1 cell surface antigen
surface





9
4
TCACACAGTG
23016
G protein-coupled receplor RDC-1
surface





8
6
GACCGCAGGA
119129
collagen, type IV, alpha 1
extracellular





8
13
GGGAGGGGTG
2399
matrix metalloproteinase 14 (membrane-inserted)
extracellular





7
14
GGGGCTGCCC
195727
tumor endothleial marker 1 precursor
surface





6
4
TTCTCCCAAA
75617
collagen, type IV, alpha 2
extracellular





6
18
CCACAGGGGA
119571
collagen, type III, alpha 1 (Ehlers-Danlos syndrom
extracellular





6
9
TCAAGTTCAC
351928

Homo sapiens mRNA full length insert cDNA Euroimage 1977059






5
10
ACCAAAAACC
172928
collagen, type I, alpha 1
extracellular





4
7
GATCAGGCCA
119571
collagen, type III, alpha 1 (Ehlers-Danlos syndrom
extracellular





4
4
AGAAACCACG
119129
collagen, type IV, alpha 1
extracellular























TABLE 8





Brain
Brain

non-EC






T/N
T/N prob
ShortTag
count
UG ID
UG description
Localization






















9
83
AAGGTTCTTC
1
89695
insulin receptor
surface






7
74
CCCTTTCACA
1
107125
PV1
surface





6
75
AGACTAGGGG
1
350065
Plexin A2
surface





4
69
CATAAACGGG
1
69954
laminin, gamma 3
extracellular





4
53
GGCCAACATT
1
36353
Homo sapiens mRNA full length insert cDNA clone EU



















TABLE 9





Short Tag
Long Tag
UG ID
UG Description



















GTACGTCCCA
GTACGTCCCACCCTGTC
183556
solute carrier family 1 (neutral amino acid transp






GCAATTTAAC
GCAATTTAACCACATTT
83974
solute carrier family 21 (prostaglandin transporte





AGGTGCGGGG
AGGTGCGGGGGGCAGAC
165439
arsA (bacterial) arsenite transporter, ATP-binding





TTTGGGGCTG
TTTGGGGCTGGCCTCAC
7476
ATPase, H+ transporting, lysosomal (vacuolar proto





CACCCTGTAC
CACCCTGTACAGTTGCC
25450
solute carrier family 29 (nucleoside transporters)





GGGTGGGCGT
GGGTGGGCGTGCAGGGA
278378
karyopherin beta 2b, transportin
















TABLE 10







gliona_tem_only_with_tag











Unigene ID
Function
Long Tag
Std Tag
Localization















Hs.101382
tumor necrosis factor, alpha-induced protein 2
ACTCAGCCCGGCTGATG
ACTCAGCCCG
cytoplasmic






Hs.102135
signal sequence receptor, delta (translocon-
GCTCTCTATGCTGACGT
GCTCTCTATG
membrane



associated protein delta)





Hs.103180
DC2 protein
AGAATGAAACTGCCGGG
AGAATGAAAC
membrane





Hs.105850
KIAA0404 protein
AAGTGGAATAAACTGCC
AAGTGGAATA
nuclear





Hs.10784
chromosome 6 open reading frame 37
TTTGAATCAGTGCTAGA
TTTGAATCAG
cytoplasmic





Hs.110802
von Willebrand factor
TTCTGCTCTTGTGCCCT
TTCTGCTCTT
extracellular





Hs.112844
maternally expressed 3
TGGGAAGTGGGCTCCTT
TGGGAAGTGG
mitochondria





Hs.11607
hypothetical protein FLJ32205
TGGGCCCGTGTCTGGCC
TGGGCCCGTG
mitochondria





Hs.118893
Melanoma associated gene
ACAACGTCCAGCTGGTG
ACAACGTCCA
extracellular





Hs.119120
E3 ubiquitin ligase SMURF1
CCCCCTGCCCCTCTGCC
CCCCCTGCCC
mitochondria





Hs.121849
microtubule-associated protein 1 light chain 3
GTCTATGCCTCCCAGGA
GTCTATGCCT
nuclear



beta





Hs.124915
hypothetical protein MGC2601
GGCTGGAGCCGCTTTGG
GGCTGGAGCC
extracellular





Hs.129780
tumor necrosis factor receptor superfamily,
CATACCTCCTGCCCCGC
CATACCTCCT
membrane



member 4





Hs.135084
cystatin C (amyloid angiopathy and cerebral
TGCCTGCACCAGGAGAC
TGCCTGCACC
extracellular



hemorrhage)





Hs.136414
UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyl-
TTCCTTGTAATCAAAGA
TTCCTTGTAA
extracellular



transferase 5





Hs.137574
coagulation factor II (thrombin) receptor-like 3
TGGCGGCAGAGGCAGAG
TGGCGGCAGA
membrane





Hs.148932
sema domain, transmembrane domain (TM), and
CCACGTGGCTGGCTGGG
CCACGTGGCT
membrane



cytoplasmic domain, (semaphorin) 6B





Hs.149152
rhophilin 1
CTGGAGGCTGCCTCGGG
CTGGAGGCTG
nuclear





Hs.149609
integrin, alpha 5 (fibronectin receptor, alpha
ATGGCAACAGATCTGGA
ATGGCAACAG
membrane



polypeptide)





Hs.151761
KIAA0100 gene product
GGTCCCCTACCCTTCCC
GGTCCCCTAC
nuclear





Hs.155048
Lutheran blood group (Auberger b antigen
CCCGCCCCCGCCTTCCC
CCCGCCCCCG
membrane



included)





Hs.155223
stanniocalcin 2
CCCGAGGCAGAGTCGGG
CCCGAGGCAG
extracellular





Hs.155396
nuclear factor (erythroid-derived 2)-like 2
CTACGTGATGAAGATGG
CTACGTGATG
nuclear





Hs.155894
protein tyrosine phosphatase, non-receptor type 1
ATGGGTTTGCATTTTAG
ATGGGTTTGC
cytoplasmic





Hs.155939
inositol polyphosphate-5-phosphatase, 145kDa
ATGGAAGTCTGCGTAAC
ATGGAAGTCT
nuclear





Hs.156351
hypothetical protein FLJ23471
TGGACAGCAGGGACCTG
TGGACAGCAG
nuclear





Hs.1600
chaperonin containing TCP1, subunit 5 (epsilon)
TCATAGAAACCTTGATT
TCATAGAAAC
cytoplasmic





Hs.160958
CDC37 cell division cycle 37 homolog
CAGCGCTGCATTGACTC
CAGCGCTGCA
cytoplasmic



(S. cerevisiae)





Hs.165983
zinc finger protein 335
CTGGGTGCCCCAGCCTG
CTGGGTGCCC
nuclear





Hs.169401
apolipoprotein E
CGACCCCACGCCACCCC
CGACCCCACG
extracellular





Hs.172813
Rho guanine nucleotide exchange factor (GEF) 7
CGCTGGGCGTCTGGGAC
CGCTGGGCGT
nuclear





Hs.1735
inhibin, beta B (activin AB beta polypeptide)
ATTAGTCAGAAACTGCC
ATTAGTCAGA
extracellular





Hs.180324
insulin-like growth factor binding protein 5
GATAGCACAGTTGTCAG
GATAGCACAG
extracellular





Hs.180610
splicing factor proline/glutamine rich
CGTACTGAGCGCTTTGG
CGTACTGAGC
nuclear



(polypyrimidine tract binding protein associated)





Hs.18069
legumain
GGGGCTTCTGTAGCCCC
GGGGCTTCTG
extracellular





Hs.180842
ribosomal protein L13
CCCGTCCGGAACGTCTA
CCCGTCCGGA
nuclear





Hs.180920
ribosomal protein S9
CCAGTGGCCCGGAGCTG
CCAGTGGCCC
mitochondria





Hs.182248
sequestosome 1
ACTGTACTCCAGCCTAG
ACTGTACTCC
cytoplasmic





Hs.1827
nerve growth factor receptor (TNFR superfamily,
AGCTCCAGACCCCCAGC
AGCTCCAGAC
membrane



member 16)





Hs.184245
SMART/HDAC1 associated repressor protein
GACTCGCAGACACCGGG
GACTCGCAGA
nuclear





Hs.184669
zinc finger protein 144 (Mel-18)
GGCCTCCAGCCACCCAC
GGCCTCCAGC
nuclear





Hs.19347
mitochondrial ribosomal protein L45
GACCAGCCTTCAGATGG
GACCAGCCTT
cytoplasmic





Hs.194654
brain-specific angiogenesis inhibitor 1
GCCCCCAGGGGCAGGAC
GCCCCCAGGG
membrane





Hs.19555
prostate tumor over expressed gene 1
GAGGATGGTGTCCTGAG
GAGGATGGTG
cytoplasmic





Hs.195851
actin, alpha 2, smooth muscle, aorta
AAGATCAAGATCATTGC
AAGATCAAGA
cytoplasmic





Hs.201671
SRY (sex determining region Y)-box 13
AGCACAGGGTCGGGGGG
AGCACAGGGT
membrane





Hs.20225
tuftelin interacting protein 11
GCCAAGTGAACTGTGGC
GCCAAGTGAA
cytoplasmic





Hs.202833
heme oxygenase (decycling) 1
CGTGGGTGGGGAGGGAG
CGTGGGTGGG
membrane





Hs.20976

Homo sapiens cDNA FLJ34888 fis, clone

CTCCCCTATGGACTGGC
CTCCCCTATG



NT2NE2017332





Hs.211600
tumor necrosis factor, alpha-induced protein 3
AGTATGAGGAAATCTCT
AGTATGAGGA
nuclear





Hs.212680
tumor necrosis factor receptor superfamily,
GCCCCCTTCCTCCCTTG
GCCCCCTTCC
membrane



member 18





Hs.21595
DNA segment on chromosome X and Y (unique) 155
GGGATTTCTGTGTCTGC
GGGATTTCTG
nuclear



expressed sequence





Hs.217493
annexin A2
CTTCCAGCTAACAGGTC
CTTCCAGCTA
nuclear





Hs.2250
leukemia inhibitory factor (cholinergic
GCCTTGGGTGACAAATT
GCCTTGGGTG
extracellular



differentiation factor)





Hs.23131
kinesin family member C3
GCCTCCCGCCACGGGGC
GCCTCCCGCG
nuclear





Hs.2340
junction plakoglobin
GTGTGGGGGGCTGGGGG
GTGTGGGGGG
nuclear





Hs.234726
serine (or cysteine) proteinase inhibitor, clade
GACTCTTCAGTCTGGAG
GACTCTTCAG
extracellular



A (alpha-1 antiproteinase, antitrypsin),



member 3





Hs.236516
C-type (calcium dependent, carbohydrate-
GCCACACCCACCGCCCC
GCCACACCCA
membrane



recognition domain) lectin, superfamily member 9





Hs.240443
multiple endocrine neoplasia I
CCAGGGCAACAGAATGA
CCAGGGCAAC
nuclear





Hs.25450
solute carrier family 29 (nucleoside
CACCCTGTACAGTTGCC
CACCCTGTAC
membrane



transporters), member 1





Hs.25590
stanniocalcin 1
GACGAATATGAATGTCA
GACGAATATG
extracellular





Hs.25590
stanniocalcin 1
CAAACTGGTCTAGGTCA
CAAACTGGTC
extracellular





Hs.25590
stanniocalcin 1
GTAATGACAGATGCAAG
GTAATGACAG
extracellular





Hs.268571
apolipoprotein C-I
TGGCCCCAGGTGCCACC
TGGCCCCAGG
extracellular





Hs.272927
Sec23 homolog A (S. cerevisiae)
AACACAATCATATGATG
AACACAATCA
cytoplasmic





Hs.274184
transcription factor binding to IGHM enhancer 3
GAGGGTATACTGAGGGG
GAGGGTATAC
nuclear





Hs.274453
likely ortholog of mouse embryonic epithelial
GGAGCCAGCTGACCTGC
GGAGCCAGCT
membrane



gene 1





Hs.278361
likely ortholog of mouse fibronectin type III
GAGCCTCAGGTGCTCCC
GAGCCTCAGG
membrane



repeat containing protein





Hs.278573
CD59 antigen p18-20 (antigen identified by
TACTTCACATACAGTGC
TACTTCACAT
extracellular



monoclonal antibodies 16.3A5, EJ16, EJ30, EL32



and G344)





Hs.286035
myosin XVB, pseudogene
CGGTGGGACCACCCTGC
CGGTGGGACC
nuclear





Hs.286035
myosin XVB, pseudogene
GGAGAAACAGCTGCTGA
GGAGAAACAG
nuclear





Hs.288203

Homo sapiens, clone IMAGE:4845226, mRNA

GCTCAGGTCTGCCGGGG
GCTCAGGTCT





Hs.288991
TNFAIP3 interacting protein 2
TCTGCACTGAGAAACTG
TCTGCACTGA
nuclear





Hs.296406
KIAA0685 gene product
TCCACGCCCTTCCTGGC
TCCACGCCCT
nuclear





Hs.29716
hypothetical protein FLJ10980
TTGCAATAGCAAAACCC
TTGCAATAGC
nuclear





Hs.297753
vimentin
TCCAAATCGATGTGGAT
TCCAAATCGA
mitochondria





Hs.29797
ribosomal protein L10
AGGGCTTCCAATGTGCT
AGGGCTTCCA
mitochondrial





Hs.299257
STs, Weakly similar to hypothetical protein
AACCTGGGAGGTGGAGG
AACCTGGGAG



FLJ20489 [Homo sapiens] [H.sapiens]





Hs.301242
likely ortholog of mouse myocytic induction/
GGCCAACATTTGGTCCA
GGCCAACATT
cytoplasmic



differentiation originator





Hs.301685
KIAA0620 protein
GGGGCTGGAGGGGGGCA
GGGGCTGGAG
membrane





Hs.302741
Homo sapiens mRNA full length insert cDNA clone
GGATGCGCAGGGGAGGC
GGATGCGCAG



EUROIMAGE 50374





Hs.318751
ESTs, Weakly similar to T21371 hypothetical
GAAGACACTTGGTTTGA
GAAGACACTT



protein F25H8.3 Caenorhabditis elegans



[C.elegans]





Hs.321231
UDP-Gal:betaGlcNAc beta 1,4-galactosyl-
GAGAGAAGAGTGATCTG
GAGAGAAGAG
extracellular



transferase, polypeptide 3





Hs.326445
v-akt murine thymoma viral oncogene homolog 2
GCAGGGTGGGGAGGGGT
GCAGGGTGGG
cytoplasmic





Hs.334604
KIAA1870 protein
TCAGTGTATTAAAACCC
TCAGTGTATT
extracellular





Hs.339283
endoplasmic reticulum associated protein 140 kDa
ATACTATAATTGTGAGA
ATACTATAAT
nuclear





Hs.34516
ceramide kinase
GCTGGTTCCTGAGTGGC
GCTGGTTCCT
cytoplasmic





Hs.348000
ESTs, Weakly similar to hypothetical protein
AGCCACTGCGCCCGGCC
AGCCACTGCG



FLJ20489 [Homo sapiens] [H.sapiens]





Hs.350065
hypothetical protein FLJ30634
AGACTAGGGGCCGGAGC
AGACTAGGGG
nuclear





Hs.352535
KIAA0943 protein
GGGACAGCTGTCTGTGG
GGGACAGCTG
cytoplasmic





Hs.352949
ESTs, Weakly similar to hypothetical protein
AACCCAGGAGGCGGAGC
AACCCAGGAG



FLJ20489 [Homo sapiens] [H.sapiens]





Hs.353002
ESTs
CAGCCTGAGGCTCTTGG
CAGCCTGAGG





Hs.353193
LOC124402
CCTCCCCTGCACCTGGG
CCTCCCCTGG
nuclear





Hs.363027

Homo sapiens cDNA FLJ39848 fis, clone

GCTTCAGTGGGGGAGAG
GCTTCAGTGG



SPLEN2014669





Hs.367653
hypothetical protein FLJ22329
TGTTTGGGGGCTTTTAG
TGTTTGGGGG
extracellular





Hs.373548

Homo sapiens cDNA: FLJ22720 fis, clone HS114320

TTTTAAATTAGGTTTTG
TTTTAAATTA





Hs.374415
ESTs
ATCTCAAAGATACACAG
ATCTCAAAGA





Hs.39619
hypothetical protein LOC57333
TTTGTGGGCAGTCAGG
CTTTGTGGGCA
extracellular





Hs39871
myosin ID
ATTGTAGACAATGAGGG
ATTGTAGACA
nuclear





Hs.400429
ESTs
GCAAAACCCTGCTCTCC
GCAAAACCCT





Hs.401975
ESTs, Weakly similar to TI7346 hypothetical
GTCTCAGTGCTGAGGCG
GTCTCAGTGC



protein DKPZp586O1624.1 - human (fragment)



[H.sapiens]





Hs.405289
ESTs, Weakly similar to hypothetical protein
AGCCACTGTGCCCGGCC
AGCCACTGTG



FLJ20378 [Homo sapiens] [H.sapiens]





Hs.406068
ubiquitin-conjugating enzyme E2M (UBC12 homolog,
TGATTAAGGTCGGCGCT
TGATTAAGGT
nuclear



yeast)





Hs.406507
sprouty homolog 4 (Drosophila)
TTACAAACAGAAAAGCT
TTACAAACAG
extracellular





Hs.41716
endothelial cell-specific molecule 1
TTTATTATTGTTCAATA
TTTATTATTG
extracellular





Hs.45006
hypothetical protein DKFZp547N157
CGGGCCTCAGGTGGCAG
CGGCCCTCAG
nuclear





Hs.4980
LIM domain binding 2
TAAAGGCACAGTGGCTC
TAAAGGCACA
nuclear





Hs.5307
synaptopodin
ATATTAGGAAGTCGGGG
ATATTAGGAA
nuclear





Hs.56205
insulin induced gene 1
TGATTAAAACAAGTTGC
TGATTAAAAC
membrane





Hs.57958
EGF-TM7-latrophilin-related protein
TTGTGCACGCATCAGTG
TTGTGCAGGC
membrane





Hs.61490
schwannomin interacting protein 1
CCTGCCTCGTAGTGAAG
CCTGCCTCGT
nuclear





Hs.61638
myosin X
CAAAACTGTTTGTTGGCC
CAAAACTGTT
nuclear





Hs.62192
coagulation factor III (thromboplastin, tissue
TAGGAAAGTAAAATGGA
TAGGAAAGTA
membrane



factor)





Hs.65238
ring finger protein 40
CTCCATCGGCTGTGAGG
CTCCATCGGC
nuclear





Hs.6657
Hermansky-Pudlak syndrome 4
CAAGCATCCCCGTTCCA
CAAGCATCCC
nuclear





Hs.6631
golgi complex associated protein 1, 60kDa
GAGTTAGGCACTTCCTG
GAGTTAGGCA
nuclear





Hs.69954
laminin, gamma 3
CATAAACGGGCACACCC
CATAAACGGG
extracellular





Hs.7187
hypothetical protein FLJ10707
TTGCCTGGGATGCTGGT
TTGCCTGGGA
nuclear





Hs.73798
macrophage migration inhibitory factor
AACGCGGCCAATGTGGG
AACGCGGCCA
cytoplasmic



(glycosylation-inhibiting factor)





Hs.73818
ubiquinol-cytochrome c reductase hinge protein
GGTTTGGCTTAGGCTGG
GGTTTGGCTT
nuclear





Hs.74471
gap junction protein, alpha 1, 43kDa
GATTTTTGTGGTGTGGG
GATTTTTGTG
membrane



(connexin 43)





Hs.74566
dihydropyrimidinase-like 3
GGCTGCCCTGGGCAGCC
GGCTGCCCTG
cytoplasmic





Hs.74602
aquaporin 1 (channel-forming integral protein,
ATGGCAACAGAAACCAA
ATGGCAACAG
membrane



28kDa)





Hs.75093
procoilagen-lysine, 2-oxoglutarate 5-dioxygenase
AGAGCAAACCGTAGTCC
AGAGCAAACC
extracellular



(lysine hydroxylase, Ehiers-Danlos syndrome type



VI)





Hs.75445
SPARC-like 1 (mastg, hevin)
TGCACTTCAAGAAAATG
TGCACTTCAA
extracellular





Hs.75736
apolipoprotein D
CCCTACCCTGTTACCTT
CCCTACCCTG
extracellular





Hs.76353
serine (or cysteine) proteinase inhibitor, clade
GGAAAAATGTTGGMTG
GGAAAAATGT
extracellular



A (alpha-1 antiproteinase, antitrypsin), member 5





Hs.7718
hypothetical protein FLJ22678
GTTTTTGCTTCAGCGGC
GTTTTTGCTT
extracellular





Hs.77313
cyclin-dependent kinase (CDC2-like) 10
GAGGACCCAACAGGAGG
GAGGACCCAA
cytoplasmic





Hs.77326
insulin-like growth factor binding protein 3
ACTGAGGAAAGGAGCTC
ACTGAGGAAA
extracellular





Hs.77573
uridine phosphorylase
TGCAGCGCCTGCGGCCT
TGCAGCGCCT
nuclear





Hs.77864
K1AA0638 protein
CTGGGGGGAAGGGACTG
CTGGGGGGAA
nuclear





Hs.77886
lamin A/C
GTGCCTGAGAGGCAGGC
GTGCCTGAGA
nuclear





Hs.77886
lamin A/C
TCACAGGGTCCCCGGGG
TCACAGGGTC
nuclear





Hs.77866
lamin A/C
GGAGGGGGCTTGAAGCC
GGAGGGGGCT
nuclear





Hs.78056
cathepsin L
GGAGGAATTCATCTTCA
GGAGGAATTC
extracellular





Hs.78531
similar to RIKEN cDNA 5730528L13 gene
GAAAGTGGCTGTCCTGG
GAAAGTGGCT
nuclear





Hs.78575
prosaposin (variant Gaucher disease and variant
TCCCTGGCTGTTGAGGC
TCCCTGGCTG
extracellular



metachromatic leukodystrophy)





Hs.82575
small nuclear ribonucleoprotein polypeptide B″
AAGATGAGGGGGCAGGC
AAGATGAGGG
nuclear





Hs.82749
transmembrane 4 superfamily member 2
CCAACAAGAATGCATTG
CCAACAAGAA
membrane





Hs.83126
TAF11 RNA polymerase II, TATA box binding protein
AAGGATGCGGTGATGGC
AAGGATGCGG
nuclear



(TBP)-associated factor, 28kDa





Hs.83169
matrix metalloproteinase 1 (interstitial
TGCAGTCACTGGTGTCA
TGCAGTCACT
extracllular



collagenase)





Hs.83384
S100 calcium binding protein, beta (neural)
GCCGTGTAGACCCTAAC
GCCGTGTAGA
cytoplasmic





Hs.83484
SRY (sex determining region Y)-box 4
CAGGCTTTTTGGCTTCC
CAGGCTTTTT
nuclear





Hs.83464
SRY (sex determining region Y)-box 4
TCCCTGGGCAGCTTCAG
TCCCTGGGCA
nuclear





Hs.63727
cleavage and polyadenylation specific factor 1,
GAGCGCAGCGAGCTAGC
GAGCGCAGCG
nuclear



160kDa





Hs.84063

Homo sapiens cDNA: FLJ23507 fis, clone LNG03128

CAGGTGGTTCTGCCATC
CAGGTGGTTC





Hs.84753
hypothetical protein FLJ12442
GCCCACATCCGCTGAGG
GCCCACATCC
cytoplasmic





Hs.89695
insulin receptor
AAGGTTCTTCTCAAGGG
AAGGTTCTTC
membrane
















TABLE 11







Glioma Repressed in Transporters










Short Tag
Long Tag
UG ID
UG Description














GGCTAATTAT**
GGCTAATTATCATCAAT
34114
ATPase, Na+/K+ transporting alpha 2(+) polypeptide






CAAAAATAAA
CAAAAATAAAAGCCGA
30246
solute carrier family 19 (thiamine transporter), m





*Transport*





**Also present in Glioma repressed list













TABLE 12







Nuclear Brain and Colon Proteins










Unigene ID
Function
OMIMID
Protein





Hs.149098
smoothelin
602127
NP_599031


Hs.197298
NS1-binding protein

AAG43485


Hs.337986
hypothetical protein MGC4677

NP_443103
















TABLE 13







Cytoplasmic Brain/Colon Proteins










Unigene ID
Function
OMIMID
Protein





Hs.327412
TEM 15, COL3A1, Homo






sapiens clone FLC1492




PRO3121 mRNA, complete cds


Hs.75721
profilin 1
176610
NP_005013
















TABLE 14







Extracellular Colon/Brain Proteins










Unigene ID
Function
OMIMID
Protein





Hs.1103
transforming growth factor, beta
190180
NP_000651



1 (Camuratl-Engelmann



disease)


Hs.111779
secreted protein, acidic,
182120
NP_003109



cysteine-rich (osteonectin)


Hs.119129
collagen, type IV, alpha 1
120130
NP_001836


Hs.119571
collagen, type III, alpha 1
120180
NP_000081



(Ehlers-Danlos syndrome type



IV, autosomal dominant


Hs.151738
matrix metalloproteinase 9
120361
NP_004985



(gelatinase B, 92 kDa



gelatinase, 92 kDa type IV



collagenase)


Hs.159263
collagen, type VI, alpha 2
120240
NP_001840


Hs.172928
collagen, type I, alpha 1
120150
NP_000079


Hs.179573
TEM 40, COL1A2 alt polyA;
120160
NP_000080



involved in tissue remodeling


Hs.75617
collagen, type IV, alpha 2
120090
NP_001837


Hs.78672
laminin, alpha 4
600133
NP_002281


Hs.821
biglycan
301870
NP_001702
















TABLE 15







Membrane Brain/Colon Proteins










Unigene ID
Function
OMIMID
Protein





Hs.125359
TEM 13, Thy-1 cell surface
188230
NP_006279



antigen


Hs.185973
degenerative spermatocyte

NP_003667



homolog, lipid desaturase



(Drosophila)


Hs.195727
TEM 1, endosialin
606064
NP_065137


Hs.23016
G protein-coupled receptor


Hs.2399
matrix metalloproteinase 14
600754
NP_004986



(membrane-inserted)


Hs.285814
sprouty homolog 4 (Drosophilia)

AAK00653


Hs.82002
endothelin receptor type B
131244
NP_000106
















TABLE 16







Brain and Colon Proteins










Unigene ID
Function
OMIMID
Protein





Hs.1103
transforming growth factor, beta 1 (Camurati-
190180
NP_000651



Engelmann disease)


Hs.111779
secreted protein, acidic, cysteine-rich
182120
NP_003109



(osteonectin)


Hs.119129
collagen, type IV, alpha 1
120130
NP_001836


Hs.119571
collagen, type III, alpha 1 (Ehlers-Danios
120180
NP_000081



syndrome type IV, autosomal dominant)


Hs.125359
TEM 13, Thy-1 cell surface antigfen
188230
NP_006279


Hs.149098
smoothelin
602127
NP_599031


Hs.151738
matrix metalloproteinase 9 (gelatinase B,
120361
NP_004985



92 kDa gelatinase, 92 kDa type IV collagenase)


Hs.159263
collagen, type VI, alpha 2
120240
NP_001840


Hs.172928
collagen, type 1, alpha 1
120150
NP_000079


Hs.179573
TEM 40, COL1A2 alt polyA; involved in tissue
120160
NP_000080



remodeling


Hs.185973
degenerative spermatocyte homolog, lipid

NP_003667



desaturase (Drosophila)


Hs.195727
TEM 1, endosialin
606064
NP_065137


Hs.197298
NS1-binding protein

AAG43485


Hs.23016
G protein-coupled receptor


Hs.2399
matrix metalloproteinase 14 (membrane-
600754
NP_004986



inserted)


Hs.285814
sprouty homolog 4 (Drosophila)

AAK00653


Hs.327412
TEM15, COL311, Homo sapiens clone



FLC1492 PRO3121 mRNA, complete cds


Hs.337986
hypotehtical protein MGC4677

NP_443103


Hs.351928

Homo sapiens mRNA full length insert cDNA




clone EUROIMAGE 1977059


Hs.356096
ESTs, Highly similar to hypothetical protein



FLJ10350 [Homo sapiens] [H. sapiens]


Hs.75617
collagen, type IV, alpha 2
120090
NP_001837


Hs.75721
profilin 1
176610
NP_005013


Hs.78672
laminin, alpha 4
600133
NP_002281


Hs.82002
endothelin receptor type B
131244
NP_000106


Hs.821
biglycan
301870
NP_001702
















TABLE 17







Additional Tumor Endothelial Markers in Brain









Unigene ID
Function






Hs.326445
v-akt murine thymoma vial oncogene homolog 2
Protein Kinase


Hs.77313
cyclin-dependent kinase (cdc2-like) 10
Protein Kinase


Hs.301242
ortholog mouse myocytic
Non-Protein Kinase



induction/differntiation originator


Hs.194654
brain-specific angiogenesis inhibitor 1
Membrane GPCR


Hs.57958
EGF-RM7 latrophilin-related protein
Membrane GPCR


Hs.148932
sema domain
Receptors with Short Cytoplasmic Tail


Hs.149609
integrin, alpha 5
Receptors with Short Cytoplasmic Tail


Hs.27836
likely ortholog of mouse fibronectin type III
Receptors with Short Cytoplasmic Tail


Hs.155048
Lutheran blood group (Auberger b antigen
Receptors with Short Cytoplasmic Tail



included)


Hs.102135
SSR4, TRAPD
Receptors with Short Cytoplasmic Tail


Hs.1827
nerve growth factor receptor (TNFR
Membrane Receptor



superfamily, member 16)


Hs.41716
insulin-like growth factor binding protein
Extracellular Growth Factors & Cytokine


Hs.2250
leukemia inhibitor factor
Extracellular Growth Factors & Cytokine


Hs.155894
protein typrosine phosphatase, nonreceptor
Cell-Selective Phosphatase



type I
















TABLE 18







Cytoplasmic GEMs










Unigene ID
Function
OMIMID
Protein





Hs.111611
ribosomal protein L27
607526
NP_000979


Hs.160958
CDC37 cell division cycle 37
605065
NP_008996



homolog (S. cerevisiae)


Hs.327412
TEM15, COLI3A1, Homo




sapiens clone FLC1492




PRO3121 mRNA, complete cds


Hs.34516
ceramide kinase

NP_073603


Hs.352535
KIAA0943 protein

BAA76787


Hs.61661
F-box only protein 32
606604
NP_478136


Hs.73798
macrophage migration
153620
NP_002406



inhibitory factor (glycosylation-



inhibiting factor)


Hs.75721
profilin 1
176610
NP_005013


Hs.83384
S100 calcium binding protein,
176990
NP_006263



beta (neural)
















TABLE 19







Nuclear GEMs










Unigene ID
Function
OMIMID
Protein





Hs.105850
KIAA0404 protein

BAA23700


Hs.110443
hypothetical protein FLJ22215

NP_073745


Hs.121849
microtubule-associated protein 1 light

NP_073729



chain 3 beta


Hs.129673
eukaryotic translation initiation factor
602641
NP_001407



4A, isoform 1


Hs.149098
smoothelin
602127
NP_599031


Hs.155396
nuclear factor (erythroid-derived 2)-like 2
600492
NP_006155


Hs.172813
Rho guanine nucleotide exchange factor
605477
NP_663788



(GEF) 7


Hs.197298
NS1-binding protein

AAG43485


Hs.211600
tumor necrosis factor, alpha-induced protein 3
191163
NP_006281


Hs.217493
annexin A2
151740



Hs.2340
junction plakoglobin
173325
NP_002221


Hs.274184
transcription factor binding to IGHM
314310
NP_006512



enhancer 3


Hs.286035
myosin XVB, pseudogene


Hs.332173
transducin-like enhancer of split 2
601041
NP_003251



(E(sp1) homolog, Drosophila)


Hs.337986
hypothetical protein MGC4677

NP_443103


Hs.339283
endoplasmic reticulum associated



protein 140 kDa


Hs.350065
hypothetical protein FLJ30634

NP_694559


Hs.65238
ring finger protein 40

NP_055586


Hs.6657
Hermansky-Pudlak syndrome 4
606682
BAB33337


Hs.75061
MARCKS-like protein
602940
NP_075385


Hs.77573
uridine phosphorylase
191730
NP_003355


Hs.77886
lamin A/C
150330
NP_005563
















TABLE 20







Membrane GEMs










Unigene ID
Function
OMIMID
Protein





Hs.107125
plasmalemina vesicle

NP_112600



associated protein


Hs.125359
TEM13, Thy-1 cell
188230
NP_006279



surface antigen


Hs.137574
coagulation factor II
602779
NP_003941



(thrombin) receptor-like 3


Hs.143897
dysterlin, limb girdle
603009
NP_003485



muscular dystrophy 2B



(autosomal recessive)


Hs.148932
sema domain,

NP_115484



transmembrane domain



(TM), and cytoplasmic



domain, (semaphorin) 6B


Hs.149609
integrin, alpha 5
135620
NP_002196



(fibronectin receptor,



alpha polypeptide)


Hs.166254
likely ortholog of rat

NP_112200



vacuole membrane



protein 1


Hs.1827
nerve growth factor
162010
NP_002498



receptor (TNFR



superfamily, member 16)


Hs.185973
degenerative

NP_003667



spermatocyte homolog,



lipid desaturase



(Drosophila)


Hs.195727
TEM1, endosialin
606064
NP_065137


Hs.202833
heme oxygenase
141250
NP_002124



(decycling) 1


Hs.23016
G protein-coupled



receptor


Hs.236516
C-type (calcium

NP_055173



dependent, carbohydrate-



recognition domain)



lectin, superfamily



member 9


Hs.2399
matrix metalloproteinase
600754
NP_004986



14 (membrane-inserted)


Hs.25450
solute carrier family 29
602193
NP_004946



(nucleoside transporters),



member 1


Hs.274453
likely ortholog of mouse

NP_060081



embryonic epithelial gene 1


Hs.277477
major histocompatibility
142840
NP_002108



complex, class I, C


Hs.27836
likely ortholog of mouse

NP_073734



fibronectin type III repeat



containing protein 1


Hs.285814
sprouty homolog 4

AAK00653



(Drosophila)


Hs.301685
KIAA0620 protein

BAA31595


Hs.62192
coagulation factor III
134390
NP_001984



(thromboplastin, tissue



factor)


Hs.74602
aquaporin 1 (channel-
110450
AAH22486



forming integral protein,



28 kDa)


Hs.77961
major histocompatibility
142830
NP_005505



complex, class I, B


Hs.79356
Lysosomal-associated
601476
NP_006753



multispanning membrane



protein-5


Hs.82002
endothelin receptor type B
131244
NP_000106


Hs.89695
insulin receptor
147670
NP_000199


Hs.97199
complement component
120577
NP_036204



1, q subcomponent,



receptor 1
















TABLE 21







Extracellular GEMS










Unigene ID
Function
OMIMID
Protein





Hs.1103
transforming growth factor,
190180
NP_000651



beta 1 (Camurati-Engelmann



disease)


Hs.110802
von Willebrand factor
193400
NP_000543


Hs.111779
secreted protein, acidic,
182120
NP_003109



cysteine-rich (osleonectin)


Hs.119129
collagen, type IV, alpha 1
120130
NP_001836


Hs.119571
collagen, type III, alpha 1
120180
NP_000081



(Ehlers-Danlos syndrome type



IV, autosomal dominant)


Hs.135084
cystatin C (amyloid angiopathy
604312
NP_000090



and cerebral hemorrhage)


Hs.136414
UDP-GlcNAc:betaGal beta-1,3-

NP_114436



N-



acetylglucosaminyltransferase 5


Hs.151738
matrix metalloproteinase 9
120361
NP_004985



(gelatinase B, 92 kDa



gelatinase, 92 kDa type IV



collagenase)


Hs.159263
collagen, type VI, alpha 2
120240
NP_001840


Hs.169401
apolipoprotein E
107741
NP_000032


Hs.172928
collagen, type I, alpha 1
120150
NP_000079


Hs.1735
inhibin, beta B (activin AB beta
147390
NP_002184



polypeptide)


Hs.179573
TEM40, COL1A2 all polyA;
120160
NP_000080



involved in tissue remodeling


Hs.180324
insulin-like growth factor
146734



binding protein 5


Hs.18069
legumain
602620
NP_005597


Hs.211573
heparan sulfate proteoglycan 2
142461
NP_005520



(perlecan)


Hs.25590
stanniocalcin 1
601185
NP_003146


Hs.268571
apolipoprotein C-I
107710


Hs.321231
UDP-Gal:betaGlcNAc beta 1,4-
604014
NP_003770



galactosyltransferase,



polypeptide 3


Hs.365706
matrix Gla protein
154870
NP_000891


Hs.367653
hypothetical protein FLJ22329


Hs.69954
laminin, gamma 3
604349
NP_006050


Hs.73817
chemokine (C-C motif) ligand 3
182283
NP_002974


Hs.75111
protease, serine, 11 (IGF
602194
NP_002766



binding)


Hs.75445
SPARC-like 1 (mast9, hevin)
606041
NP_004675


Hs.75617
collagen, type IV, alpha 2
120090
NP_001837


Hs.75736
apolipoprotein D
107740
NP_001638


Hs.7718
hypothetical protein FLJ22678

NP_078812


Hs.77326
insulin-like growth factor
146732
NP_000589



binding protein 3


Hs.78575
prosaposin (variant Gaucher
176801
NP_002769



disease and variant



metachromatic



leukodystrophy)


Hs.78672
laminin, alpha 4
600133
NP_002281


Hs.82085
serine (or cysteine) proteinase
173360
NP_000593



inhibitor, clade E (nexin,



plasminogen activator inhibitor



type 1), member 1


Hs.821
biglycan
301870
NP_001702


Hs.83169
matrix metalloproteinase 1
120353
NP_002412



(interstitial collagenase)


Hs.90107
adhesion regulating molecule 1

NP_008933
















TABLE 22







Brain tumor markers unsorted










Unigene ID
Function
OMIMID
Protein





Hs.105850
KIAA0404 protein

BAA23700


Hs.107125
plasmalemma vesicle

NP_112600



associated protein


Hs.1103
transforming growth factor,
190180
NP_000651



beta 1 (Camurati-Engelmann



disease)


Hs.110443
hypothetical protein FLJ22215

NP_073745


Hs.110802
von Willebrand factor
193400
NP_000543


Hs.111611
ribosomal protein L27
607526
NP_000979


Hs.111779
secreted protein, acidic,
182120
NP_003109



cysteine-rich (osteonectin)


Hs.11607
hypothetical protein FLJ32205

NP_689774


Hs.119129
collagen, type IV, alpha 1
120130
NP_001836


Hs.119571
collagen, type III, alpha 1
120180
NP_000081



(Ehlers-Danlos syndrome type



IV, autosomal dominant)


Hs.121849
microtubule-associated

NP_073729



protein 1 light chain 3 beta


Hs.125359
TEM13, Thy-1 cell surface
188230
NP_006279



antigen


Hs.127824
ESTs, Weakly similar to



CA28_HUMAN Collagen



alpha 2(VIII) chain



(Endothelial collagen)



[H. sapiens]


Hs.129673
eukaryotic translation initiation
602641
NP_001407



factor 4A, isoform 1


Hs.135084
cystatin C (amyloid
604312
NP_000090



angiopathy and cerebral



hemorrhage)


Hs.136414
UDP-GlcNAc:betaGal beta-

NP_114436



1,3-N-



acetylglucosaminyltransferase 5


Hs.137574
coagulation factor II
602779
NP_003941



(thrombin) receptor-like 3


Hs.143897
dysferlin, limb girdle muscular
603009
NP_003485



dystrophy 2B (autosomal



recessive)


Hs.148932
sema domain,

NP_115484



transmembrane domain (TM),



and cytoplasmic domain,



(semaphorin) 6B


Hs.149098
smoothelin
602127
NP_599031


Hs.149609
integrin, alpha 5 (fibronectin
135620
NP_002196



receptor, alpha polypeptide)


Hs.151738
matrix metalloproteinase 9
120361
NP_004985



(gelatinase B, 92 kDa



gelatinase, 92 kDa type IV



collagenase)


Hs.155396
nuclear factor (erythroid-
600492
NP_006155



derived 2)-like 2


Hs.159263
collagen, type VI, alpha 2
120240
NP_001840


Hs.160958
CDC37 cell division cycle 37
605065
NP_008996



homolog (S. cerevisiae)


Hs.166254
likely ortholog of rat vacuole

NP_112200



membrane protein 1


Hs.169401
apolipoprotein E
107741
NP_000032


Hs.172813
Rho guanine nucleotide
605477
NP_663788



exchange factor (GEF) 7


Hs.172928
collagen, type I, alpha 1
120150
NP_000079


Hs.1735
inhibin, beta B (activin AB
147390
NP_002184



beta polypeptide)


Hs.179573
TEM40, COL1A2 alt polyA;
120160
NP_000080



involved in tissue remodeling


Hs.180324
insulin-like growth factor
146734



binding protein 5


Hs.18069
legumain
602620
NP_005597


Hs.180920
ribosomal protein S9
603631


Hs.1827
nerve growth factor receptor
162010
NP_002498



(TNFR superfamily, member



16)


Hs.185973
degenerative spermatocyte

NP_003667



homolog, lipid desaturase



(Drosophila)


Hs.195727
TEM1, endosialin
606064
NP_065137


Hs.197298
NS1-binding protein

AAG43485


Hs.202833
heme oxygenase (decycling) 1
141250
NP_002124


Hs.20976

Homo sapiens cDNA




FLJ34888 fis, clone



NT2NE2017332


Hs.211573
heparan sulfate proteoglycan
142461
NP_005520



2 (perlecan)


Hs.211600
tumor necrosis factor, alpha-
191163
NP_006281



induced protein 3


Hs.217493
annexin A2
151740


Hs.23016
G protein-coupled receptor


Hs.2340
junction plakoglobin
173325
NP_002221


Hs.236516
C-type (calcium dependent,

NP_055173



carbohydrate-recognition



domain) lectin, superfamily



member 9


Hs.2399
matrix metalloproteinase 14
600754
NP_004986



(membrane-inserted)


Hs.25450
solute carrier family 29
602193
NP_004946



(nucleoside transporters).



member 1


Hs.25590
stanniocalcin 1
601185
NP_003146


Hs.268571
apolipoprotein C-I
107710


Hs.274184
transcription factor binding to
314310
NP_006512



IGHM enhancer 3


Hs.274453
likely ortholog of mouse

NP_060081



embryonic epithelial gene 1


Hs.277477
major histocompatibility
142840
NP_002108



complex, class I, C


Hs.27836
likely ortholog of mouse

NP_073734



fibronectin type III repeat



containing protein 1


Hs.285814
sprouty homolog 4

AAK00653



(Drosophila)


Hs.286035
myosin XVB, pseudogene


Hs.288203

Homo sapiens, clone




IMAGE: 4845226, mRNA


Hs.29797
ribosomal protein L10
312173
NP_115617


Hs.299257
ESTs, Weakly similar to



hypothetical protein FLJ20489



[Homo sapiens] [H. sapiens]


Hs.301685
KIAA0620 protein

BAA31595


Hs.302741

Homo sapiens mRNA full




length insert cDNA clone



EUROIMAGE 50374


Hs.318751
ESTs, Weakly similar to



T21371 hypothetical protein



F25H8.3 - Caenorhabditis




elegans [C. elegans]



Hs.321231
UDP-Gal:betaGlcNAc beta
604014
NP_003770



1,4-galactosyltransferase,



polypeptide 3


Hs.327412
TEM15, COL3A1, Homo




sapiens clone FLC1492




PRO3121 mRNA, complete



cds


Hs.332173
transducin-like enhancer of
601041
NP_003251



split 2 (E(sp1) homolog,




Drosophila)



Hs.337986
hypothetical protein MGC4677

NP_443103


Hs.339283
endoplasmic reticulum



associated protein 140 kDa


Hs.34516
ceramide kinase

NP_073603


Hs.350065
hypothetical protein FLJ30634

NP_694559


Hs.351928

Homo sapiens mRNA full




length insert cDNA clone



EUROIMAGE 1977059


Hs.352535
KIAA0943 protein

BAA76787


Hs.352949
ESTs, Weakly similar to



hypothetical protein FLJ20489



[Homo sapiens] [H. sapiens]


Hs.356096
ESTs, Highly similar to



hypothetical protein FLJ10350



[Homo sapiens] [H. sapiens]


Hs.363027

Homo sapiens cDNA




FLJ39848 fis, clone



SPLEN2014669


Hs.365706
matrix Gla protein
154870
NP_000891


Hs.367653
hypothetical protein FLJ22329


Hs.374415
ESTs


Hs.380983
ESTs, Highly similar to



ITB1_HUMAN Integrin beta-1



precursor (Fibronectin



receptor beta subunit) (CD29)



(Integrin VLA-4 beta subunit)



[H. sapiens]


Hs.400429
ESTs


Hs.401975
ESTs, Weakly similar to



T17346 hypothetical protein



DKFZp586O1624.1 - human



(fragment) [H. sapiens]


Hs.61661
F-box only protein 32
606604
NP_478136


Hs.62192
coagulation factor III
134390
NP_001984



(thromboplastin, tissue factor)


Hs.65238
ring finger protein 40

NP_055586


Hs.6657
Hermansky-Pudlak syndrome 4
606682
BAB33337


Hs.69954
laminin, gamma 3
604349
NP_006050


Hs.73798
macrophage migration
153620
NP_002406



inhibitory factor (glycosylation-



inhibiting factor)


Hs.73817
chemokine (C-C motif) ligand 3
182283
NP_002974


Hs.74602
aquaporin 1 (channel-forming
110450
AAH22486



integral protein, 28 kDa)


Hs.75061
MARCKS-like protein
602940
NP_075385


Hs.75111
protease, serine, 11 (IGF
602194
NP_002766



binding)


Hs.75445
SPARC-like 1 (mast9, hevin)
606041
NP_004675


Hs.75617
collagen, type IV, alpha 2
120090
NP_001837


Hs.75721
profilin 1
176610
NP_005013


Hs.75736
apolipoprotein D
107740
NP_001638


Hs.7718
hypothetical protein FLJ22678

NP_078812


Hs.77326
insulin-like growth factor
146732
NP_000589



binding protein 3


Hs.77573
uridine phosphorylase
191730
NP_003355


Hs.77886
lamin A/C
150330
NP_005563


Hs.77961
major histocompatibility
142830
NP_005505



complex, class I, B


Hs.78575
prosaposin (variant Gaucher
176801
NP_002769



disease and variant



metachromatic



leukodystrophy)


Hs.78672
laminin, alpha 4
600133
NP_002281


Hs.79356
Lysosomal-associated
601476
NP_006753



multispanning membrane



protein-5


Hs.82002
endothelin receptor type B
131244
NP_000106


Hs.82085
serine (or cysteine) proteinase
173360
NP_000593



inhibitor, clade E (nexin,



plasminogen activator



inhibitor type 1), member 1


Hs.821
biglycan
301870
NP_001702


Hs.83169
matrix metalloproteinase 1
120353
NP_002412



(interstitial collagenase)


Hs.83384
S100 calcium binding protein,
176990
NP_006263



beta (neural)


Hs.84063

Homo sapiens cDNA:




FLJ23507 fis, clone



LNG03128


Hs.89695
insulin receptor
147670
NP_000199


Hs.90107
adhesion regulating molecule 1

NP_008933


Hs.97199
complement component 1, q
120577
NP_036204



subcomponent, receptor 1








Claims
  • 1. A method to aid in diagnosing glioma, comprising the steps of: detecting an expression product of at least one gene in a first brain tissue sample suspected of being neoplastic wherein said at least one gene is selected from the group consisting of signal sequence receptor, delta (translocon-associated protein delta); DC2 protein; KIAA0404 protein; symplekin; Huntingtin interacting protein I; plasmalemma vesicle associated protein; KIAA0726 gene product; latexin protein; transforming growth factor, beta 1; hypothetical protein FLJ22215; Rag C protein; hypothetical protein FLJ23471; N-myristoyltransferase 1; hypothetical protein dJ1181N3.1; ribosomal protein L27; secreted protein, acidic, cysteine-rich (osteonectin); Hs 111988; Hs 112238; laminin, alpha 5; protective protein for beta-galactosidase (galactosialidosis); Melanoma associated gene; Melanoma associated gene; E3 ubiquitin ligase SMURF1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; gene predicted from cDNA with a complete coding sequence; Thy-1 cell surface antigen; Hs 127824; GTP binding protein 2; Homo sapiens mRNA; cDNA DKFZp586D0918 (from clone DKFZp586D0918); cutaneous T-cell lymphoma-associated tumor antigen se20-4; differentially expressed nucleolar TGF-beta1 target protein (DENTT); dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); smoothelin; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); putative translation initiation factor; retinoic acid induced 14; matrix metalloproteinase 9 (gelatinase B, 92 kD gelatinase, 92 kD type IV collagenase); Lutheran blood group (Auberger b antigen included); stanniocalcin 2; nuclear factor (erythroid-derived 2)-like 2; protein tyrosine phosphatase, non-receptor type 1; integrin, alpha 10; collagen, type VI, alpha 2; chromosome 21 open reading frame 25; CDC37 (cell division cycle 37, S. cerevisiae, homolog); Hs 16450; Rho guanine nucleotide exchange factor (GEF) 7; creatine kinase, brain; hypothetical protein FLJ10297; hypothetical protein FLJ10350; TNF-induced protein; tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein); cofilin 1 (non-muscle); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); v-ets avian erythroblastosis virus E26 oncogene homolog 1; protease, cysteine, 1 (legumain); ribosomal protein L13; chromosome 22 open reading frame 5; zinc finger protein 144 (Mel-18); degenerative spermatocyte (homolog Drosophila; lipid desaturase); eukaryotic translation initiation factor 2C, 2; mitochondrial ribosomal protein L45; prostate tumor over expressed gene 1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (14.5 kD, B14.5a); glioma endothelial marker 1 precursor; NS1-binding protein; ribosomal protein L38; tuftelin-interacting protein; HLA class II region expressed gene KE2; translocase of inner mitochondrial membrane 17 homolog A (yeast); sudD (suppressor of bimD6, Aspergillus nidulans) homolog; heparan sulfate proteoglycan 2 (perlecan); SEC24 (S. cerevisiae) related gene family, member A; NADH dehydrogenase (ubiquinone) Fe—S protein 7 (20 kD) (NADH-coenzyme Q reductase); DNA segment on chromosome X and Y (unique) 155 expressed sequence; annexin A2; Homo sapiens clone 24670 mRNA sequence; hypothetical protein; matrix metalloproteinase 10 (stromelysin 2); KIAA1049 protein; G protein-coupled receptor; hypothetical protein FLJ20401; matrix metalloproteinase 14 (membrane-inserted); KIAA0470 gene product; solute carrier family 29 (nucleoside transporters), member 1; stanniocalcin 1; stanniocalcin 1; stanniocalcin 1; tumor suppressor deleted in oral cancer-related 1; tumor suppressor deleted in oral cancer-related 1; apolipoprotein C—I; glutathione peroxidase 4 (phospholipid hydroperoxidase); Hs 272106; transcription factor binding to IGHM enhancer 3; hypothetical protein DKFZp762A227; hypothetical protein FLJ22362; CD59 antigen p18-20 (antigen identified by monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344); PRO0628 protein; melanoma-associated antigen recognised by cytotoxic T lymphocytes; LOC88745; Homo sapiens beta-1,3-galactosyltransferase-6 (B3GALT6) mRNA, complete cds; sprouty (Drosophila) homolog 4; sprouty (Drosophila) homolog 4; Homo sapiens mRNA; cDNA DKFZp434E1515 (from clone DKFZp434E1515); coactosin-like protein; hypothetical protein FLJ21865; Hs296234; KIAA0685 gene product; hypothetical protein FLJ10980; ribosomal protein L10; ribosomal protein S19; Hs 299251; Huntingtin interacting protein K; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 50374; Hs 311780; Hs 212191; v-akt murine thymoma viral oncogene homolog 2; Hs 328774; transducin-like enhancer of split 2, homolog of Drosophila E(sp1); KIAA1870 protein; ribosomal protein L10a; peptidyiprolyl isomerase A (cyclophilin A); Hs 344224; hypothetical protein FLJ23239; hypothetical protein DKFZp761H221; KIAA1887 protein; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 701679; Homo sapiens cDNA FLJ30634 fis, clone CTONG2002453; Homo sapiens cDNA FLJ32203 fis, clone PLACE6003038, weakly similar to ZINC FINGER PROTEIN 84; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1035904; hypothetical protein L0057333; myosin ID; plexin B2; lectin, galactoside-binding, soluble, 8 (galectin 8); double ring-finger protein, Dorfin; DKFZP434B 168 protein; LIM domain binding 2; integrin beta 4 binding protein; synaptopodin; Hs 54828; insulin induced gene 1; acetyl LDL receptor; SREC; excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence); hypothetical protein FLJ22329; schwannomin-interacting protein 1; PTEN induced putative kinase 1; myosin X; Homo sapiens cDNA FLJ32424 fis, clone SKMUS2000954, moderately similar to Homo sapiens F-box protein Fbx25 (FBX25) 97; golgi phosphoprotein 1; splicing factor, arginine/serine-rich 6; laminin, gamma 3; cysteine-rich protein 2; U6 snRNA-associated Sm-like protein LSm7; hypothetical protein FLJ10707; Homo sapiens, Similar to RIKEN cDNA 2310012N15 gene, clone IMAGE:3342825, mRNA, partial cds; macrophage migration inhibitory factor (glycosylation-inhibiting factor); ubiquinol-cytochrome c reductase hinge protein; gap junction protein, alpha 1, 43 kD (connexin 43); dihydropyrimidinase-like 3; aquaporin 1 (channel-forming integral protein, 28 kD); protein expressed in thyroid; macrophage myristoylated alanine-rich C kinase substrate; procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI); protease, serine, 11 (IGF binding); 24-dehydrocholesterol reductase; collagen, type IV, alpha 2; profilin 1; apolipoprotein D; hyaluronoglucosaminidase 2; hypothetical protein FLJ22678; quiescin Q6; ras homolog gene family, member A; ras homolog gene family, member A; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; uridine phosphorylase; KIAA0638 protein; B7 homolog 3; lamin A/C; lamin A/C; lamin A/C; regulator of G-protein signalling 12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8; Homo sapiens, Similar to RIKEN cDNA 5730528L13 gene, clone MGC:17337 IMAGE:4213591, mRNA, complete cds; prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy); laminin, alpha 4; transcription elongation factor A (SII), 1; lectin, galactoside-binding, soluble, 3 binding protein; ribosomal protein S16; glycophorin C (Gerbich blood group); endothelin receptor type B; serine (or cysteine) proteinase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1; biglycan; small nuclear ribonucleoprotein polypeptide B″; transmembrane 4 superfamily member 2; TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28 kD; lysyl oxidase-like 2; SRY (sex determining region Y)-box 4; SOX4 SRY (sex determining region Y)-box 4; SRY (sex determining region Y)-box 4; actin related protein 2/3 complex, subunit 2 (34 kD); Homo sapiens cDNA: FLJ23507 fis, clone LNG03128; hypothetical protein FLJ12442; Fas (TNFRSF6)-associated via death domain; mitogen-activated protein kinase kinase kinase 11; TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal); insulin receptor; cell membrane glycoprotein, 110000M(r) (surface antigen); Homo sapiens cDNA FLJ11863 fis, clone HEMBA1006926; jagged 1 (Alagille syndrome); KIAA0304 gene product; pre-B-cell leukemia transcription factor 2; Homo sapiens cDNA FLJ31238 fis, clone KIDNE2004864; p53-induced protein; complement component 1, q subcomponent, receptor 1; complement component 1, q subcomponent, receptor 1; apolipoprotein E; chemokine (C—C motif) ligand 3; coagulation factor II (thrombin) receptor-like 3; coagulation factor III (thromboplastin, tissue factor); collagen, type I, alpha 1; collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant); C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; cystatin C (amyloid angiopathy and cerebral hemorrhage); endoplasmic reticulum associated protein 140 kDa; ESTs; ESTs; ESTs, Highly similar to hypothetical protein FLJ10350 [Homo sapiens] [H.sapiens]; ESTs, Highly similar to ITB1_HUMAN Integrin beta-1 precursor (Fibronectin receptor beta subunit) (CD29) (Integrin VLA-4 beta subunit) [H.sapiens]; ESTs, Weakly similar to hypothetical protein FLJ20489 [Homo sapiens] [H.sapiens]; ESTs, Weakly similar to T17346 hypothetical protein DKFZp586O1624.1-human (fragment) [H.sapiens]; ESTs, Weakly similar to T21371 hypothetical protein F25H8.3—Caenorhabditis elegans [C.elegans]; eukaryotic translation initiation factor 4A, isoform 1; heme oxygenase (decycling) 1; Hermansky-Pudlak syndrome 4; Homo sapiens cDNA FLJ34888 fis, clone NT2NE2017332; Homo sapiens cDNA FLJ39848 fis, clone SPLEN2014669; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1977059; Homo sapiens, clone IMAGE:4845226, mRNA; hypothetical protein FLJ22329; hypothetical protein FLJ32205; hypothetical protein MGC4677; inhibin, beta B (activin AB beta polypeptide); insulin-like growth factor binding protein 5; junction plakoglobin; KIAA0620 protein; KIAA0943 protein;likely ortholog of rat vacuole membrane protein 1; Lysosomal-associated multispanning membrane protein-5; major histocompatibility complex, class I, B; major histocompatibility complex, class I, C; matrix Gla protein; matrix metalloproteinase 1 (interstitial collagenase); microtubule-associated protein I light chain 3 beta; nerve growth factor receptor (TNFR superfamily, member 16); ribosomal protein S9; ring finger protein 40; S100 calcium binding protein, beta (neural); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; SPARC-like 1 (mast9, hevin); tumor necrosis factor, alpha-induced protein 3; UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 3; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5; von Willebrand factor; v-akt murine thymoma vial oncogene homolog 2; cyclin-dependent kinase (cdc2-like) 10; ortholog mouse myocytic induction/differentiation originator; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16); insulin-like growth factor binding protein; leukemia inhibitory factor; protein tyrosine phosphatase, nonreceptor type I; and Homo sapiens, clone IMAGE:3908182, mRNA, partial cds;andcomparing expression of the at least one gene in the first brain tissue sample with expression of the at least one gene in a second brain tissue sample which is normal, wherein increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample identifies the first brain tissue sample as likely to be neoplastic.
  • 2. The method of claim 1 wherein the increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample is at least two-fold higher.
  • 3. The method of claim 1 wherein the increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample is at least five-fold higher.
  • 4. The method of claim 1 wherein the increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample is at least ten-fold higher.
  • 5. The method of claim 1 wherein the expression product is RNA.
  • 6. The method of claim 1 wherein the expression product is protein.
  • 7. The method of claim 1 wherein the first and second tissue samples are from a human.
  • 8. The method of claim 1 wherein the first and second tissue samples are from the same human.
  • 9. The method of claim 6 wherein the step of detecting is performed using a Western blot.
  • 10. The method of claim 6 wherein the step of detecting is performed using an immunoassay.
  • 11. The method of claim 6 wherein the step of detecting is performed using an immunohistochemical assay.
  • 12. The method of claim 5 wherein the step of detecting is performed using SAGE.
  • 13. The method of claim 5 wherein the step of detecting is performed using hybridization to a microarray.
  • 14. A method of treating a glioma, comprising the step of: contacting cells of the glioma with an antibody, wherein the antibody specifically binds to an extracellular epitope of a protein selected from the group consisting of plasmalemma vesicle associated protein; KIAA0726 gene product; osteonectin: laminin, alpha 5; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; Thy-1 cell surface antigen; dysferlin, limb girdle muscular dystrophy 2B; integrin, alpha 5; matrix metalloproteinase 9; Lutjheran blood group, integrink, alpha 10, collagen, type VI, alpha 2; glioma endothelial marker I precursor; translocase of inner mitochondrial membrane 17 homolog A; heparan sulfate proteoglycan 2; annexin A2; matrix metalloproteinase 10; G protein-coupled receptor; matrix metalloproteinase 14; solute carrier family 29, member 1; CD59 antigen p18-20; KIAA 1870 protein; plexin B2; lectin, glactoside-binding, soluble, 8; integrin beta 4 binding protein; acetyl LDL receptor; laminin, gamma 3; macrophage migration inhibitory factor; gap junction p roein, alpha 1, 43 kD; aquaporin 1; protease, serine, 11; collagen, type IV, alpha 2; apolipoprotein D; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; regulator of G-protein signaling 12; prosaposin; laminin, alpha 4; lectin, galactoside-binding, soluble, 3 binding protein; glycophorin C; endothelin receptor type B; biglycan; transmembrane 4 superfamilyh member 2; lysyl osidase-like 2; TEK tyrosine kinase, endothelial; insulin receptore; cell membrane glycoprotein, 110000M(r); jagged 1; plasmalemma vesicle associated protein; TEM13, Thy-1 cell surface antigen; coagulation factor II (thrombin) receptor-like 3; dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); likely ortholog of rat vacuole membrane protein 1; nerve growth factor receptor (TNFR superfamily, member 16); degenerative spermatocyte homolog, lipid desaturase (Drosophila); TEM1, endosialin; heme oxygenase (decycling) 1; G protein-coupled receptor; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; matrix metalloproteinase 14 (membrane-inserted); solute carrier family 29 (nucleoside transporters), member 1; likely ortholog of mouse embryonic epithelial gene 1; major histocompatibility complex, class I, C; likely ortholog of mouse fibronectin type III repeat containing protein 1; sprouty homolog 4 (Drosophila); KIAA0620 protein; coagulation factor III (thromboplastin, tissue factor); aquaporin 1 (channel-forming integral protein, 28 kDa); major histocompatibility complex, class I, B; Lysosomal-associated multispanning membrane protein-5; endothelin receptor type B; insulin receptor; complement component 1, q subcomponent, receptor 1; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16) and complement component 1, q subcomponent, receptor 1; whereby immune destruction of cells of the glioma is triggered.
  • 15. The method of claim 14 wherein the antibody is conjugated to a diagnostic or therapeutic reagent.
  • 16. The method of claim 14 wherein the glioma is multidrug-sensitive.
  • 17. The method of claim 15 wherein the reagent is a chemotherapeutic agent.
  • 18. The method of claim 15 wherein the reagent is a cytotoxin.
  • 19. The method of claim 15 wherein the reagent is a non-radioactive label.
  • 20. The method of claim 15 wherein the reagent is a radioactive compound.
  • 21. The method of claim 14 wherein the glioma is in a human.
  • 22. A method of identifying a test compound as a potential anti-cancer or anti-glioma drug, comprising the step of: contacting a test compound with a cell which expresses at least one gene selected from the group consisting of signal sequence receptor, delta (translocon-associated protein delta); DC2 protein; KIAA0404 protein; symplekin; Huntingtin interacting protein I; plasmalemma vesicle associated protein; KIAA0726 gene product; latexin protein; transforming growth factor, beta 1; hypothetical protein FLJ22215; Rag C protein; hypothetical protein FLJ23471; N-myristoyltransferase 1; hypothetical protein dJ1181N3.1; ribosomal protein L27; secreted protein, acidic, cysteine-rich (osteonectin); Hs 111988; Hs 112238; laminin, alpha 5; protective protein for beta-galactosidase (galactosialidosis); Melanoma associated gene; Melanoma associated gene; E3 ubiquitin ligase SMURF1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; gene predicted from cDNA with a complete coding sequence; Thy-1 cell surface antigen; Hs 127824; GTP binding protein 2; Homo sapiens mRNA; cDNA DKFZp586D0918 (from clone DKFZp586D0918); cutaneous T-cell lymphoma-associated tumor antigen se20-4; differentially expressed nucleolar TGF-beta1 target protein (DENTT); dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); smoothelin; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); putative translation initiation factor; retinoic acid induced 14; matrix metalloproteinase 9 (gelatinase B, 92 kD gelatinase, 92 kD type IV collagenase); Lutheran blood group (Auberger b antigen included); stanniocalcin 2; nuclear factor (erythroid-derived 2)-like 2; protein tyrosine phosphatase, non-receptor type 1; integrin, alpha 10; collagen, type VI, alpha 2; chromosome 21 open reading frame 25; CDC37 (cell division cycle 37, S. cerevisiae, homolog); Hs 16450; Rho guanine nucleotide exchange factor (GEF) 7; creatine kinase, brain; hypothetical protein FLJ10297; hypothetical protein FLJ10350; TNF-induced protein; tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein); cofilin 1 (non-muscle); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); v-ets avian erythroblastosis virus E26 oncogene homolog 1; protease, cysteine, 1 (legumain); ribosomal protein L13; chromosome 22 open reading frame 5; zinc finger protein 144 (Mel-18); degenerative spermatocyte (homolog Drosophila; lipid desaturase); eukaryotic translation initiation factor 2C, 2; mitochondrial ribosomal protein L45; prostate tumor over expressed gene 1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (14.5 kD, B14.5a); glioma endothelial marker 1 precursor; NS1-binding protein; ribosomal protein L38; tuftelin-interacting protein; HLA class II region expressed gene KE2; translocase of inner mitochondrial membrane 17 homolog A (yeast); sudD (suppressor of bimD6, Aspergillus nidulans) homolog; heparan sulfate proteoglycan 2 (perlecan); SEC24 (S. cerevisiae) related gene family, member A; NADH dehydrogenase (ubiquinone) Fe—S protein 7 (20 kD) (NADH-coenzyme Q reductase); DNA segment on chromosome X and Y (unique) 155 expressed sequence; annexin A2; Homo sapiens clone 24670 mRNA sequence; hypothetical protein; matrix metalloproteinase 10 (stromelysin 2); KIAA1049 protein; G protein-coupled receptor; hypothetical protein FLJ20401; matrix metalloproteinase 14 (membrane-inserted); KIAA0470 gene product; solute carrier family 29 (nucleoside transporters), member 1; stanniocalcin 1; stanniocalcin 1; stanniocalcin 1; tumor suppressor deleted in oral cancer-related 1; tumor suppressor deleted in oral cancer-related 1; apolipoprotein C—I; glutathione peroxidase 4 (phospholipid hydroperoxidase); Hs 272106; transcription factor binding to IGHM enhancer 3; hypothetical protein DKFZp762A227; hypothetical protein FLJ22362; CD59 antigen p18-20 (antigen identified by monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344); PRO0628 protein; melanoma-associated antigen recognised by cytotoxic T lymphocytes; LOC88745; Homo sapiens beta-1,3-galactosyltransferase-6 (B3GALT6) mRNA, complete cds; sprouty (Drosophila) homolog 4; sprouty (Drosophila) homolog 4; Homo sapiens mRNA; cDNA DKFZp434E1515 (from clone DKFZp434E1515); coactosin-like protein; hypothetical protein FLJ21865; Hs296234; KIAA0685 gene product; hypothetical protein FLJ10980; ribosomal protein L10; ribosomal protein S19; Hs 299251; Huntingtin interacting protein K; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 50374; Hs 311780; Hs 212191; v-akt murine thymoma viral oncogene homolog 2; Hs 328774; transducin-like enhancer of split 2, homolog of Drosophila E(sp1); KIAA1870 protein; ribosomal protein L10a; peptidylprolyl isomerase A (cyclophilin A); Hs 344224; hypothetical protein FLJ23239; hypothetical protein DKFZp761H221; KIAA1887 protein; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 701679; Homo sapiens cDNA FLJ30634 fis, clone CTONG2002453; Homo sapiens cDNA FLJ32203 fis, clone PLACE6003038, weakly similar to ZINC FINGER PROTEIN 84; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1035904; hypothetical protein L0057333; myosin ID; plexin B2; lectin, galactoside-binding, soluble, 8 (galectin 8); double ring-finger protein, Dorfin; DKFZP434B168 protein; LIM domain binding 2; integrin beta 4 binding protein; synaptopodin; Hs 54828; insulin induced gene 1; acetyl LDL receptor; SREC; excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence); hypothetical protein FLJ22329; schwannomin-interacting protein 1; PTEN induced putative kinase 1; myosin X; Homo sapiens cDNA FLJ32424 fis, clone SKMUS2000954, moderately similar to Homo sapiens F-box protein Fbx25 (FBX25) 97; golgi phosphoprotein 1; splicing factor, arginine/serine-rich 6; laminin, gamma 3; cysteine-rich protein 2; U6 snRNA-associated Sm-like protein LSm7; hypothetical protein F1110707; Homo sapiens, Similar to RIKEN cDNA 2310012N15 gene, clone IMAGE:3342825, mRNA, partial cds; macrophage migration inhibitory factor (glycosylation-inhibiting factor); ubiquinol-cytochrome c reductase hinge protein; gap junction protein, alpha 1, 43 kD (connexin 43); dihydropyrimidinase-like 3; aquaporin 1 (channel-forming integral protein, 28 kD); protein expressed in thyroid; macrophage myristoylated alanine-rich C kinase substrate; procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI); protease, serine, 11 (IGF binding); 24-dehydrocholesterol reductase; collagen, type IV, alpha 2; profilin 1; apolipoprotein D; hyaluronoglucosaminidase 2; hypothetical protein FLJ22678; quiescin Q6; ras homolog gene family, member A; ras homolog gene family, member A; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; uridine phosphorylase; KIAA0638 protein; B7 homolog 3; lamin A/C; lamin A/C; lamin A/C; regulator of G-protein signalling 12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8; Homo sapiens, Similar to RIKEN cDNA 5730528L13 gene, clone MGC:17337 IMAGE:4213591, mRNA, complete cds; prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy); laminin, alpha 4; transcription elongation factor A (SII), 1; lectin, galactoside-binding, soluble, 3 binding protein; ribosomal protein S16; glycophorin C (Gerbich blood group); endothelin receptor type B; serine (or cysteine) proteinase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1; biglycan; small nuclear ribonucleoprotein polypeptide B″; transmembrane 4 superfamily member 2; TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28 kD; lysyl oxidase-like 2; SRY (sex determining region Y)-box 4; SOX4 SRY (sex determining region Y)-box 4; SRY (sex determining region Y)-box 4; actin related protein 2/3 complex, subunit 2 (34 kD); Homo sapiens cDNA: FLJ23507 fis, clone LNG03128; hypothetical protein FLJ12442; Fas (TNFRSF6)-associated via death domain; mitogen-activated protein kinase kinase kinase 11; TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal); insulin receptor; cell membrane glycoprotein, 110000M(r) (surface antigen); Homo sapiens cDNA FLJ11863 fis, clone HEMBA1006926; jagged 1 (Alagille syndrome); KIAA0304 gene product; pre-B-cell leukemia transcription factor 2; Homo sapiens cDNA FLJ31238 fis, clone KIDNE2004864; p53-induced protein; complement component 1, q subcomponent, receptor 1; complement component 1, q subcomponent, receptor 1; apolipoprotein E; chemokine (C—C motif) ligand 3; coagulation factor II (thrombin) receptor-like 3; coagulation factor III (thromboplastin, tissue factor); collagen, type I, alpha 1; collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant); C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; cystatin C (amyloid angiopathy and cerebral hemorrhage); endoplasmic reticulum associated protein 140 kDa; ESTs; ESTs; ESTs, Highly similar to hypothetical protein FLJ10350 [Homo sapiens] [H.sapiens]; ESTs, Highly similar to ITB1_HUMAN Integrin beta-1 precursor (Fibronectin receptor beta subunit) (CD29) (Integrin VLA-4 beta subunit) [H.sapiens]; ESTs, Weakly similar to hypothetical protein FLJ20489 [Homo sapiens] [H.sapiens]; ESTs, Weakly similar to T17346 hypothetical protein DKFZp58601624.1-human (fragment) [H.sapiens]; ESTs, Weakly similar to T21371 hypothetical protein F25H8.3—Caenorhabditis elegans [C.elegans]; eukaryotib translation initiation factor 4A, isoform 1; heme oxygenase (decycling) 1; Hermansky-Pudlak syndrome 4; Homo sapiens cDNA FLJ34888 fis, clone NT2NE2017332; Homo sapiens cDNA FLJ39848 fis, clone SPLEN2014669; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1977059; Homo sapiens, clone IMAGE:4845226, mRNA; hypothetical protein FLJ22329; hypothetical protein FLJ32205; hypothetical protein MGC4677; inhibin, beta B (activin AB beta polypeptide); insulin-like growth factor binding protein 5; junction plakoglobin; KIAA0620 protein; KIAA0943 protein; likely ortholog of rat vacuole membrane protein 1; Lysosomal-associated multispanning membrane protein-5; major histocompatibility complex, class I, B; major histocompatibility complex, class I, C; matrix Gla protein; matrix metalloproteinase 1 (interstitial collagenase); microtubule-associated protein 1 light chain 3 beta; nerve growth factor receptor (TNFR superfamily, member 16); ribosomal protein S9; ring finger protein 40; S100 calcium binding protein, beta (neural); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; SPARC-like 1 (mast9, hevin); tumor necrosis factor, alpha-induced protein 3; UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 3; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5; von Willebrand factor; v-akt murine thymoma vial oncogene homolog 2; cyclin-dependent kinase (cdc2-like) 10; ortholog mouse myocytic induction/differentiation originator; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16); insulin-like growth factor binding protein; leukemia inhibitory factor; protein tyrosine phosphatase, nonreceptor type I; and Homo sapiens, clone IMAGE:3908182, mRNA, partial cds;monitoring an expression product of the at least one gene; andidentifying the test compound as a potential anti-cancer drug if it decreases the expression of the at least one gene.
  • 23. The method of claim 22 wherein the cell is a human cell.
  • 24. The method of claim 22 wherein the cell is a glioma cell.
  • 25. The method of claim 22 wherein the cell is a human glioma cell.
  • 26. The method of claim 22 wherein the expression product is RNA.
  • 27. The method of claim 22 wherein the expression product is protein.
  • 28. The method of claim 22 wherein the cell overexpresses the at least one gene relative to a normal cell of the same tissue.
  • 29. The method of claim 22 wherein expression of at least two of said genes is monitored.
  • 30. The method of claim 22 wherein expression of at least three of said genes is monitored.
  • 31. The method of claim 22 wherein expression of at least four of said genes is monitored.
  • 32. The method of claim 22 wherein the test compound is identified if the decrease in expression is at least 50%.
  • 33. The method of claim 22 wherein the test compound is identified if the decrease in expression is at least 80%.
  • 34. The method of claim 22 wherein the decrease in expression is at least 90%.
  • 35. The method of claim 22 wherein the test compound is identified as an anti-glioma drug.
  • 36. A method to aid in diagnosing glioma, comprising the steps of: detecting an mRNA of at least one gene in a first brain tissue sample suspected of being neoplastic wherein said at least one gene is identified by a tag selected from the group consisting of SEQ ID NO: 1-32; andcomparing expression of the at least one gene in the first brain tissue sample with expression of the at least one gene in a second brain tissue sample which is normal, wherein increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample identifies the first brain tissue sample as likely to be neoplastic.
  • 37. The method of claim 36 wherein the increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample is at least two-fold higher.
  • 38. The method of claim 36 wherein the increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample is at least five-fold higher.
  • 39. The method of claim 36 wherein the increased expression of the at least one gene in the first brain tissue sample relative to the second tissue sample is at least ten-fold higher.
  • 40. The method of claim 36 wherein the first and second tissue samples are from a human.
  • 41. The method of claim 36 wherein the first and second tissue samples are from the same human.
  • 42. The method of claim 36 wherein the step of detecting is performed using a Western blot.
  • 43. The method of claim 36 wherein the step of detecting is performed using an immunoassay.
  • 44. The method of claim 36 wherein the step of detecting is performed using an immunohistochemical assay.
  • 45. The method of claim 36 wherein the step of detecting is performed using SAGE.
  • 46. The method of claim 36 wherein the step of detecting is performed using hybridization to a microarray.
  • 47. A method of identifying a test compound as a potential anti-cancer or anti-glioma drug, comprising the step of: contacting a test compound with a cell which expresses an mRNA of at least one gene identified by a tag selected from the group consisting of SEQ ID NO: 1-32;monitoring an mRNA of the at least one gene; andidentifying the test compound as a potential anti-cancer drug if it decreases the expression of the at least one gene.
  • 48. The method of claim 47 wherein the cell is a human cell.
  • 49. The method of claim 47 wherein the cell is a glioma cell.
  • 50. The method of claim 47 wherein the cell is a human glioma cell.
  • 51. The method of claim 47 wherein the expression product is RNA.
  • 52. The method of claim 47 wherein the expression product is protein.
  • 53. The method of claim 47 wherein the cell overexpresses the at least one gene relative to a normal cell of the same tissue.
  • 54. The method of claim 47 wherein expression of at least two of said genes is monitored.
  • 55. The method of claim 47 wherein expression of at least three of said genes is monitored.
  • 56. The method of claim 47 wherein expression of at least four of said genes is monitored.
  • 57. The method of claim 47 wherein the test compound is identified if the decrease in expression is at least 50%.
  • 58. The method of claim 47 wherein the test compound is identified if the decrease in expression is at least 80%.
  • 59. The method of claim 47 wherein the decrease in expression is at least 90%.
  • 60. The method of claim 47 wherein the test compound is identified as an anti-glioma drug.
  • 61. A method to induce an immune response to glioma, comprising: administering to a mammal a protein or nucleic acid encoding a protein selected from the group consisting of: signal sequence receptor, delta (translocon-associated protein delta); DC2 protein; KIAA0404 protein; symplekin; Huntingtin interacting protein I; plasmalemma vesicle associated protein; KIAA0726 gene product; latexin protein; transforming growth factor, beta 1; hypothetical protein FLJ22215; Rag C protein; hypothetical protein FLJ23471; N-myristoyltransferase 1; hypothetical protein dJ1181N3.1; ribosomal protein L27; secreted protein, acidic, cysteine-rich (osteonectin); Hs 111988; HS 112238; laminin, alpha 5; protective protein for beta-galactosidase (galactosialidosis); Melanoma associated gene; Melanoma associated gene; E3 ubiquitin ligase SMURF1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; collagen, type IV, alpha 1; insulin-like growth factor binding protein 7; gene predicted from cDNA with a complete coding sequence; Thy-1 cell surface antigen; Hs 127824; GTP binding protein 2; Homo sapiens mRNA; cDNA DKFZp586D0918 (from clone DKFZp586D0918); cutaneous T-cell lymphoma-associated tumor antigen se20-4; differentially expressed nucleolar TGF-beta1 target protein (DENTT); dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive); smoothelin; integrin, alpha 5 (fibronectin receptor, alpha polypeptide); putative translation initiation factor; retinoic acid induced 14; matrix metalloproteinase 9 (gelatinase B, 92 kD gelatinase, 92 kD type IV collagenase); Lutheran blood group (Auberger b antigen included); stanniocalcin 2; nuclear factor (erythroid-derived 2)-like 2; protein tyrosine phosphatase, non-receptor type 1; integrin, alpha 10; collagen, type VI, alpha 2; chromosome 21 open reading frame 25; CDC37 (cell division cycle 37, S. cerevisiae, homolog); Hs 16450; Rho guanine nucleotide exchange factor (GEF) 7; creatine kinase, brain; hypothetical protein FLJ10297; hypothetical protein FLJ10350; TNF-induced protein; tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein); cofilin 1 (non-muscle); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); splicing factor proline/glutamine rich (polypyrimidine tract-binding protein-associated); v-ets avian erythroblastosis virus E26 oncogene homolog 1; protease, cysteine, 1 (legumain); ribosomal protein L13; chromosome 22 open reading frame 5; zinc finger protein 144 (Mel-18); degenerative spermatocyte (homolog Drosophila; lipid desaturase); eukaryotic translation initiation factor 2C, 2; mitochondrial ribosomal protein L45; prostate tumor over expressed gene 1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (14.510, B14.5a); glioma endothelial marker 1 precursor; NS1-binding protein; ribosomal protein L38; tuftelin-interacting protein; HLA class II region expressed gene KE2; translocase of inner mitochondrial membrane 17 homolog A (yeast); sudD (suppressor of bimD6, Aspergillus nidulans) homolog; heparan sulfate proteoglycan 2 (perlecan); SEC24 (S. cerevisiae) related gene family, member A; NADH dehydrogenase (ubiquinone) Fe—S protein 7 (20 kD) (NADH-coenzyme Q reductase); DNA segment on chromosome X and Y (unique) 155 expressed sequence; annexin A2; Homo sapiens clone 24670 mRNA sequence; hypothetical protein; matrix metalloproteinase 10 (stromelysin 2); KIAA1049 protein; G protein-coupled receptor; hypothetical protein FLJ20401; matrix metalloproteinase 14 (membrane-inserted); KIAA0470 gene product; solute carrier family 29 (nucleoside transporters), member 1; stanniocalcin 1; stanniocalcin 1; stanniocalcin 1; tumor suppressor deleted in oral cancer-related 1; tumor suppressor deleted in oral cancer-related 1; apolipoprotein C—I; glutathione peroxidase 4 (phospholipid hydroperoxidase); Hs 272106; transcription factor binding to IGHM enhancer 3; hypothetical protein DKFZp762A227; hypothetical protein FLJ22362; CD59 antigen p18-20 (antigen identified by monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344); PRO0628 protein; melanoma-associated antigen recognised by cytotoxic T lymphocytes; LOC88745; Homo sapiens beta-1,3-galactosyltransferase-6 (B3GALT6) mRNA, complete cds; sprouty (Drosophila) homolog 4; sprouty (Drosophila) homolog 4; Homo sapiens mRNA; cDNA DKFZp434E1515 (from clone DKFZp434E1515); coactosin-like protein; hypothetical protein FLJ21865; Hs296234; KIAA0685 gene product; hypothetical protein FLJ10980; ribosomal protein L10; ribosomal protein S19; Hs 299251; Huntingtin interacting protein K; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 50374; Hs 311780; Hs 212191; v-akt murine thymoma viral oncogene homolog 2; Hs 328774; transducin-like enhancer of split 2, homolog of Drosophila E(sp1); KIAA1870 protein; ribosomal protein L10a; peptidylprolyl isomerase A (cyclophilin A); Hs 344224; hypothetical protein FLJ23239; hypothetical protein DKFZp761H221; KIAA1887 protein; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 701679; Homo sapiens cDNA F1130634 fis, clone CTONG2002453; Homo sapiens cDNA FLJ32203 fis, clone PLACE6003038, weakly similar to ZINC FINGER PROTEIN 84; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1035904; hypothetical protein L0057333; myosin ID; plexin B2; lectin, galactoside-binding, soluble, 8 (galectin 8); double ring-finger protein, Dorfin; DKFZP434B168 protein; LIM domain binding 2; integrin beta 4 binding protein; synaptopodin; Hs 54828; insulin induced gene 1; acetyl LDL receptor; SREC; excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence); hypothetical protein FLJ22329; schwannomin-interacting protein 1; PTEN induced putative kinase 1; myosin X; Homo sapiens cDNA FLJ32424 fis, clone SKMUS2000954, moderately similar to Homo sapiens F-box protein Fbx25 (FBX25) 97; golgi phosphoprotein 1; splicing factor, arginine/serine-rich 6; laminin, gamma 3; cysteine-rich protein 2; U6 snRNA-associated Sm-like protein LSm7; hypothetical protein FLJ10707; Homo sapiens, Similar to RIKEN cDNA 2310012N15 gene, clone IMAGE:3342825, mRNA, partial cds; macrophage migration inhibitory factor (glycosylation-inhibiting factor); ubiquinol-cytochrome c reductase hinge protein; gap junction protein, alpha 1, 43 kD (connexin 43); dihydropyrimidinase-like 3; aquaporin 1 (channel-forming integral protein, 28 kD); protein expressed in thyroid; macrophage myristoylated alanine-rich C kinase substrate; procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI); protease, serine, 11 (IGF binding); 24-dehydrocholesterol reductase; collagen, type IV, alpha 2; profilin 1; apolipoprotein D; hyaluronoglucosaminidase 2; hypothetical protein FLJ22678; quiescin Q6; ras homolog gene family, member A; ras homolog gene family, member A; plasminogen activator, urokinase; insulin-like growth factor binding protein 3; uridine phosphorylase; KIAA0638 protein; B7 homolog 3; lamin A/C; lamin A/C; lamin A/C; regulator of G-protein signalling 12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8; Homo sapiens, Similar to RIKEN cDNA 5730528L13 gene, clone MGC:17337 IMAGE:4213591, mRNA, complete cds; prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy); laminin, alpha 4; transcription elongation factor A (SII), 1; lectin, galactoside-binding, soluble, 3 binding protein; ribosomal protein S16; glycophorin C (Gerbich blood group); endothelin receptor type B; serine (or cysteine) proteinase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1; biglycan; small nuclear ribonucleoprotein polypeptide B″; transmembrane 4 superfamily member 2; TAF 11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28 kD; lysyl oxidase-like 2; SRY (sex determining region Y)-box 4; SOX4 SRY (sex determining region Y)-box 4; SRY (sex determining region Y)-box 4; actin related protein 2/3 complex, subunit 2 (34 kD); Homo sapiens cDNA: FLJ23507 fis, clone LNG03128; hypothetical protein FLJ12442; Fas (TNFRSF6)-associated via death domain; mitogen-activated protein kinase kinase kinase 11; TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal); insulin receptor; cell membrane glycoprotein, 110000M(r) (surface antigen); Homo sapiens cDNA FLJ11863 fis, clone HEMBA1006926; jagged 1 (Alagille syndrome); KIAA0304 gene product; pre-B-cell leukemia transcription factor 2; Homo sapiens cDNA FLJ31238 fis, clone KIDNE2004864; p53-induced protein; complement component 1, q subcomponent, receptor 1; complement component 1, q subcomponent, receptor 1; apolipoprotein E; chemokine (C—C motif) ligand 3; coagulation factor II (thrombin) receptor-like 3; coagulation factor III (thromboplastin, tissue factor); collagen, type I, alpha 1; collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant); C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9; cystatin C (amyloid angiopathy and cerebral hemorrhage); endoplasmic reticulum associated protein 140 kDa; ESTs; ESTs; ESTs, Highly similar to hypothetical protein FLJ10350 [Homo sapiens] [H.sapiens]; ESTs, Highly similar to ITB1 HUMAN Integrin beta-1 precursor (Fibronectin receptor beta subunit) (CD29) (Integrin VLA-4 beta subunit) [H.sapiens]; ESTs, Weakly similar to hypothetical protein FLJ20489 [Homo sapiens] [H.sapiens]; ESTs, Weakly similar to T17346 hypothetical protein DKFZp58601624.1-human (fragment) [H.sapiens]; ESTs, Weakly similar to T21371 hypothetical protein F25H8.3—Caenorhabditis elegans [C.elegans]; eukaryotic translation initiation factor 4A, isoform 1; heme oxygenase (decycling) 1; Hermansky-Pudlak syndrome 4; Homo sapiens cDNA FLJ34888 fis, clone NT2NE2017332; Homo sapiens cDNA FLJ39848 fis, clone SPLEN2014669; Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1977059; Homo sapiens, clone IMAGE:4845226, mRNA; hypothetical protein FLJ22329; hypothetical protein FLJ32205; hypothetical protein MGC4677; inhibin, beta B (activin AB beta polypeptide); insulin-like growth factor binding protein 5; junction plakoglobin; KIAA0620 protein; KIAA0943 protein; likely ortholog of rat vacuole membrane protein 1; Lysosomal-associated multispanning membrane protein-5; major histocompatibility complex, class I, B; major histocompatibility complex, class I, C; matrix Gla protein; matrix metalloproteinase 1 (interstitial collagenase); microtubule-associated protein 1 light chain 3 beta; nerve growth factor receptor (TNFR superfamily, member 16); ribosomal protein S9; ring finger protein 40; 5100 calcium binding protein, beta (neural); sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B; SPARC-like 1 (mast9, hevin); tumor necrosis factor, alpha-induced protein 3; UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide 3; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5; von Willebrand factor; v-akt murine thymoma vial oncogene homolog 2; cyclin-dependent kinase (cdc2-like) 10; ortholog mouse myocytic induction/differentiation originator; brain-specific angiogenesis inhibitor 1; EGF-TM7 latrophilin-related protein; sema domain; integrin, alpha 5; likely ortholog of mouse fibronectin type III; Lutheran blood group (Auberger b antigen included); SSR4, TRAPD; nerve growth factor receptor (TNFR superfamily, member 16); insulin-like growth factor binding protein; leukemia inhibitory factor; protein tyrosine phosphatase, nonreceptor type I; and Homo sapiens, clone IMAGE:3908182, mRNA, partial cds, whereby an immune response to the protein is induced.
  • 62. The method of claim 61 wherein a protein is administered.
  • 63. The method of claim 61 wherein a nucleic acid is administered.
  • 64. The method of claim 63 wherein the nucleic acid is administered intramuscularly.
  • 65. The method of claim 62 further comprising administering an immune adjuvant to the mammal.
  • 66. The method of claim 61 wherein the mammal has a glioma.
  • 67. The method of claim 61 wherein the mammal has had a glioma surgically removed.
Parent Case Info

This application claims the benefit of provisional application Ser. Nos. 60/403,390 filed Aug. 15, 2002 and 60/458,978 filed Apr. 1, 2003. The disclosures of each are expressly incorporated herein.

Provisional Applications (2)
Number Date Country
60403390 Aug 2002 US
60458978 Apr 2003 US
Divisions (1)
Number Date Country
Parent 10524432 Sep 2005 US
Child 12616600 US