Determining cancer-linked genes and therapeutic targets using molecular cytogenetic methods

Information

  • Patent Application
  • 20070059697
  • Publication Number
    20070059697
  • Date Filed
    April 15, 2004
    20 years ago
  • Date Published
    March 15, 2007
    17 years ago
Abstract
Methods for identifying potential therapeutic agents, such as anti-tumor agents, based on their modulation of the expression of specified genes, especially genes mapping to specific chromosomal regions, are disclosed. Also described are methods for diagnosing cancerous, or potentially cancerous, conditions as a result of the expression, or patterns of expression, of such genes, including detecting changes in levels of gene copy number and/or level of amplification of the said gene, or sets of genes, to detect and/or diagnose the cancer. Methods for detecting or determining functionally related genes, as well as methods for treating cancer based on targeting expression products of such genes, determining genes involved in the cancerous process and the success and/or response rates and survival statistics for cancer patients on treatment are encompassed by the invention. Also encompassed are methods involving determining the modulated expression of the genes in these regions of interest (ROIs) as pharmacodynamic/pharmacogenetic /surrogate markers and/or for patient profiling prior to accrual for clinical trials/treatments based on the identification of these genes as validated gene/drug targets in various cancer tissue types.
Description
FIELD OF THE INVENTION

The present invention relates to identification of genes whose disruption and/or change in expression is useful to distinguish cancerous from non-cancerous tissue and serve as potential therapeutic targets, pharmacodynamic/pharmacogenetic/surrogate and prognostic and diagnostic markers, and which genes are identified by high resolution Comparative Genomic Hybridization (CGH) and Spectral Karyotyping (SKY)/fluorescent in situ hybridization (FISH) analysis of DNA and chromosomes of various cancer cell lines and primary and metastatic tumor samples combined with gene expression analysis of these cells and tissues.


BACKGROUND OF THE INVENTION

Chromosomal abnormalities have been identified in most cancer cells.


Conventional chromosome banding techniques allow for the detection of specific chromosomal defects in tumor cells but interpretation of the banding pattern is sometimes difficult, particularly when complex chromosomal rearrangements or subtle abnormalities are present. In recent years, new techniques, such as CGH and SKY, based on fluorescent in situ hybridization (FISH) (Pinkel et al., Proc Nat Acad Sci USA 85:9138-42 (1988)) have been developed to overcome the limitations of conventional chromosome banding. CGH measures intensities of fluorescently labeled tumor DNA and normal DNA following hybridization to normal chromosomes (Kallioniemi et al., Science 258:818-21 (1992)). Gain or loss of copy number of a particular chromosome or chromosome region in the tumor DNA is determined by the relative intensity of a fluorescence ratio. SKY utilizes a cocktail of chromosome probes, fluorescently labeled to specify each chromosome, which is hybridized to tumor chromosomes in an effort to identify numerical and structural abnormalities in the tumor cell (Schröck et al., Science 273:494-7 (1996)). CGH and SKY have been used to identify chromosomal regions that harbor genes significant to the process of tumor initiation or progression.


BRIEF SUMMARY OF THE INVENTION

In one aspect the present invention relates to a set of genes that have been localized within human chromosomal regions of interest (ROI) that have been identified by molecular cytogenetic techniques.


In one aspect, the present invention relates to a method for diagnosing cancer in a mammal, especially a human patient, comprising determining amplification of a gene in the genome of a mammal wherein said gene is a gene of Table 1.


In a preferred embodiment thereof, the cancer is a member selected from breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.


In another preferred embodiment thereof, 3. The method of claim 1 wherein said gene of Table 1 is a gene that encodes the same gene product as a polynucleotide selected from the polynucleotides of SEQ ID NO: 1-805 and 855-923.


In another embodiment, the present invention relates to a method for diagnosing cancer or a pre-cancerous condition in a mammal, comprising:


(a) obtaining a cell or tissue sample from a mammal, especially a human patient, suspected of having cancer or a pre-cancerous condition and determining for said sample the gene copy number of a gene of Table 1;


(b) comparing said gene copy number of step (a) to the gene copy number of the same gene from a sample of a corresponding cell or tissue from a mammal of the same species not having cancer of the type being diagnosed whereby a higher gene copy number determined in step (a) relative to that in step (b) indicates the presence of a cancer or pre-cancerous condition in the mammal of step (a) and results in a diagnosis of cancer or a pre-cancerous condition in said mammal.


In a preferred embodiment of the methods of the invention, said molecule is a member selected from an antisense DNA, an antisense RNA, a ribozyme and an siRNA.


In another embodiment, the present invention relates to a method for identifying an agent having therapeutic activity in a human patient in need of said therapeutic activity, comprising:


(a) determining in a sample from a patient the level of a gene product encoded by a gene of Table 1 prior to administering a test compound to said patient;


(b) administering said test compound to said patient;


(c) determining in a sample from said patient the level of a gene product encoded by the same the gene as in step (a)


wherein a decrease in the level of said gene product in step (c) relative to step (a) identifies said test compound as an agent having therapeutic activity.


In a further embodiment, the present invention relates to a method for identifying an antineoplastic agent, comprising:


(a) contacting a test compound with a cell that expresses a gene of Table 1; and


(b) determining a change in gene expression as a result of said contacting;


whereby said change in said gene expression identifies said test compound as an antineoplastic agent.


The present invention also relates to a method for determining the cancerous status of a cell, comprising determining elevated expression in said cell of a gene of Table 1 wherein elevated expression of said gene indicates that said cell is cancerous.


In an additional embodiment, the present invention relates to a method for identifying a compound as an anti-neoplastic agent, comprising:


(a) contacting a test compound with a polypeptide encoded by a gene of Table 1,


(b) determining a change in a biological activity of said polypeptide due to said contacting,


wherein a change in activity identifies said test compound as an agent having antineoplastic activity.


In a preferred embodiment of the foregoing, the polypeptide is an enzyme selected from kinase, protease, peptidase, phosphodiesterase, phosphatase, dehydrogenase, reductase, carboxylase. transferase, deacetylase and polymerase.


The present invention also relates to a method for identifying an anti-neoplastic agent comprising contacting a cancerous cell with a compound found to have anti-neoplastic activity in other the methods of the invention under conditions promoting the growth of said cell and detecting a change in the activity of said cancerous cell.


The present invention further relates to a method for treating cancer comprising contacting a cancerous cell with an agent having affinity for an expression product of a gene of Table 1 and in an amount effective to cause a reduction in cancerous activity of said cell.


The present invention also contemplates a method for monitoring the progress of cancer therapy in a patient comprising monitoring in a patient undergoing cancer therapy the expression of a gene of Table 1.


In addition, the present invention encompasses a method for determining the likelihood of success of cancer therapy in a patient, comprising monitoring in a patient undergoing cancer therapy the expression of a gene of Table 1 wherein a decrease in said expression prior to completion of said cancer therapy is indicative of a likelihood of success of said cancer therapy.


In another embodiment, the present invention relates to a method for producing test data with respect to the anti-neoplastic activity of a compound comprising:


(a) identifying a test compound as having anti-neoplastic activity using other methods of the invention;


(b) producing test data with respect to the anti-neoplastic activity of said test compound sufficient to identify the chemical structure of said test compound.


Additionally, the present invention encompasses a method for determining the progress of a treatment for cancer in a patent afflicted therewith, following commencement of a cancer treatment on said patient, comprising:


(a) determining in said patient a change in expression of one or more genes of Table 1; and


(b) determining a change in expression of said gene compared to expression of said one or more determined genes prior to said cancer treatment;


wherein said change in expression indicates progress of said treatment thereby determining the progress of said treatment.


SEQUENCE LISTING ON CD-ROM ONLY

The sequences disclosed herein as SEQ ID NO: 1-923 in the sequence listing are contained on compact disc (CD-ROM) only, which accompanies this application and the contents of said CD-ROMs are hereby incorporated by reference in their entirety. These sequence numbers also appear in Table where all sequences are referred to as consecutive serial numbers for reference purposes only.


DETAILED SUMMARY OF THE INVENTION

The present invention relates to a set of genes that are amplified and/or over-expressed genes in cancer cell lines and have been localized to various chromosomal regions of interest. These genes have been identified through a combination of CGH, SKY, expression analysis and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Such genes are both markers and potential therapeutic targets for cancer, in particular breast, colon, lung and prostate malignancies. In addition, the amplified nature of such genes provides a means of diagnosing a cancerous condition, or predisposition to a cancerous conditions, by determining the amplification of one or more of such genes in a patient afflicted with, or predisposed toward, or otherwise at risk of developing, cancer.


In accordance with the present invention, a number of genes have been localized to a chromosomal regions of interest as identified in Table 1 (serial number 1-229 (breast), 230-440 (colon), 441-656 (lung) and 657-805 (prostate), serial number 806-923 (transcript or protein)). The invention also includes any subsets of these. As described herein, these sequences include DNA sequences of SEQ ID NO: 1-805, transcripts with the sequences of SEQ ID NO: 855-923, and proteins/polypeptides with amino acid sequences of SEQ ID NO: 806-854.


Briefly, the procedures used to identify the genes disclosed herein may be summarized as follows:


For CGH analysis, based on detailed molecular cytogenetic characterizations, the following data sets are generated, which may include regions reported in the public domain as well as unique regions not previously known.

  • 1. A map of chromosomal regions involved in consistent, recurrent and high level genomic gains (i.e., amplifications) for a representative cancer cell line or tumor type (e.g. colon, prostate, breast and lung) that can be recognized as a pattern/signature for a given tumor type.
  • 2. A map of chromosomal regions containing genomic losses (i.e., deletions) in each tumor type and individual cell line to be examined.
  • 3. Levels of intensities of gains and losses categorized for entry into a database.
  • 4. A comparison of the patterns of gains and losses between the clinical samples (e.g. colon xenografts) and cell lines (e.g., colon) of matched Stages and Grades.
  • 5. A comparison of the patterns of gains and losses between primary prostate tumor cell lines (e.g., CPDR lines) and metastatic prostate tumor cell lines (e.g., DU 145, PC3 and LNCaP).


In accordance with the present invention, for SKY analysis, data sets were generated according to the following steps:

  • 1. Identification and development of a database of novel chromosomal rearrangements in epithelial cancer cell lines.
  • 2. Identification of novel translocations involving specific chromosomes or chromosomal regions
  • 3. Reconciliation of SKY and CGH analysis on the same cell line as a verification of the combined findings.


Combining genomic DNA analysis of gains and losses in the tumor cell lines/clinical samples with cDNA expression analysis from matched tumor types displayed on a genome template from the Golden Path genome browser using a Spotfire™ analysis tool:

  • 1. A pattern of gene expression on a U-95 Affymatix chip set obtained via the Gene Logic database was used to generate differential gene expression profiles between samples sets containing normal and. malignant tissues from colon, prostate, lung, breast and various cell lines.
  • 2. A Spotfire™ visualization tool was developed that allowed the generation of a list of all the genes that are present in the Golden Path within the clustered regions of gains/losses for each cell type/tumor type to generate the gene sets to include in the HITS platform
  • 3. The following algorithm was employed:
    • i) Match chromosomal regions of amplification/gains defined by CGH with the location of genes/ESTs on an Affymatix chip as mapped to a Golden Path genome template.
    • ii) Identify genes/ESTs over-expressed in tumor tissue compared to normal tissue in said chromosomal regions using the Gene Logic database.
    • iii) Compile data on cell lines of a particular tumor type and different tumor types showing clusters of genomic gains and losses at certain chromosomal regions.
    • iv) Pick BACs that span the chromosomal regions consistently gained and containing over-expressed genes in an effort to positionally clone novel cancer genes (oncogenes and genes in relevant pathways)
    • v) Validate the identified genes by
      • A) Picking STS markers that identify the gene sequence and quantify the relative copy number in genomic DNA and RNA across a panel of tumor cell lines.
      • B) Develop probes for FISH on chromosomes from tumor cell lines and primary tumor tissue micro-arrays.
  • 4. The expression data from tumor cell lines that have undergone SKY/CGH analysis was used to pick candidate genes to validate as individual targets in functional genomic assays and in-vivo assays and for use in the transcriptional assay platform.


In accordance with the present invention, over-expression of cellular genes is conveniently monitored in model cellular systems using cell lines (such as is used in the example below), primary cells, or tissue samples maintained in growth media. For different purposes, these may be treated with compounds at one or more different concentrations to assay for modulating agents. Thus, cellular. RNAs were isolated from the cells or cultures as an indicator of selected gene expression. The cellular RNAs were then divided and subjected to analysis that detected the presence and/or quantity of specific RNA transcripts, which transcripts were then amplified for detection purposes using standard methodologies, such as reverse transcriptase polymerase chain reaction (RT-PCR). The levels of specific RNA transcripts, including their presence or absence, were determined. When used for identification of modulating agents, such as ant-neoplastic agents, a metric is derived for the type and degree of response of the treated sample compared to control samples.


In accordance with the foregoing, the genes identified as being amplified and/or over-expressed, which can include increased copy number thereof, in cancerous cells are localized in chromosomal regions of interest as identified in Table 1 (serial number 1-229 (breast), 230440 (colon), 441-656 (lung) and 657-805 (prostate); for polypeptide SEQ ID NOs, see Table 1, serial number 806-923 (transcript or protein)).


These genes may be utilized to characterize, the cancerous, or non-cancerous, status of cells, or tissues. The methods of the invention may be used with a variety of cell lines or with primary samples from tumors maintained in vitro under suitable culture conditions for varying periods of time, or in situ in suitable animal models.


The genes disclosed herein are expressed at levels in cancer cells that are different from the expression levels in non-cancer cells. These genes as identified in Table 1 are amplified in cancer cells relative to non-cancer cells of corresponding tissues, especially breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.


In accordance with the foregoing, the present invention relates to a method for diagnosing cancer in a mammal, comprising determining amplification of a gene in the genome of a mammal wherein said gene is a gene of Table 1.


In a preferred embodiment thereof, said gene of Table 1 is a gene that encodes the same gene product as a polynucleotide selected from the polynucleotides of SEQ ID NO: 1-805 and 855-923. In a further preferred embodiment, said mammal is a human patient.


The present invention is also directed to a method for diagnosing cancer or a pre-cancerous condition in a mammal, preferably a human patient, comprising:


(a) obtaining a cell or tissue sample from a mammal suspected of having cancer or a pre-cancerous condition and determining for said sample the gene copy number of a gene of Table 1;


(b) comparing said gene copy number of step (a) to the gene copy number of the same gene from a sample of a corresponding cell or tissue from a mammal of the same species not having cancer of the type being diagnosed


whereby a higher gene copy number determined in step (a) relative to that in step (b) indicates the presence of a cancer or pre-cancerous condition in the mammal of step (a) and results in a diagnosis of cancer or a pre-cancerous condition in said mammal.


In specific embodiments, the cancer to be diagnosed is one or more of breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.


Preferably, the gene of Table 1 is a gene that encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.


The present invention is also directed to a method of inhibiting cancer, or a pre-cancerous condition, in a mammalian cell, comprising contacting said cell with a molecule that inhibits function of a gene of Table 1. Preferably, the gene of Table 1 is a gene that encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923. In a specific embodiment thereof, said molecule inhibits gene function by binding to said gene. In other embodiments, the molecule inhibits gene function by binding to an RNA encoded by said gene or inhibits gene function by binding to polypeptide encoded by said gene. Preferably, the molecule is a member selected from an antisense DNA, an antisense RNA, a ribozyme and an siRNA. Also preferred is where the cancer is a member selected from breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.


The invention contemplates that such contacting occurs in vivo.


The invention also relates to a method for identifying an agent having therapeutic activity in a human patient in need of said therapeutic activity, comprising:


(a) determining in a sample from a patient the level of a gene product encoded by a gene of Table 1 prior to administering a test compound to said patient;


(b) administering said test compound to said patient;


(c) determining in a sample from said patient the level of a gene product encoded by the same the gene as in step (a)


wherein a decrease in the level of said gene product in step (c) relative to step (a) identifies said test compound as an agent having therapeutic activity.


Preferably, said therapeutic activity is anticancer activity and said cancer is one or more of breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.


Also preferred is where said gene product is an RNA or a polypeptide, especially where an activity of the polypeptide is determined, preferably an enzyme activity. In specific embodiments, said gene of Table 1 is a gene that encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923, as well as where said molecule is a member selected from an antisense DNA, an antisense RNA, a ribozyme and an siRNA.


The present invention also relates to a method for identifying an antineoplastic agent, comprising:


(a) contacting a test compound with a cell that expresses a gene of Table 1; and


(b) determining a change in gene expression as a result of said contacting;


whereby said change in said gene expression identifies said test compound as an antineoplastic agent.


Most preferred is where the change in expression is a decrease in expression. The contacting may occur in vivo. Also preferred is where said gene of Table 1 encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923 and where said molecule is a member selected from an antisense DNA, an antisense RNA, ribozyme, an siRNA, a small organic molecule and an antibody.


The present invention also relates to a method for determining the cancerous status of a cell, comprising determining elevated expression in said cell of a gene of Table 1 wherein elevated expression of said gene indicates that said cell is cancerous. Preferably, wherein said elevated expression is an elevated copy number of the gene and wherein said gene of Table 1 encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855 -923.


The present invention further relates to a method for identifying a compound as an anti-neoplastic agent, comprising:


(a) contacting a test compound with a polypeptide encoded by a gene of Table 1,


(b) determining a change in a biological activity of said polypeptide due to said contacting,


wherein a change in activity identifies said test compound as an agent having antineoplastic activity.


Preferably, said gene of Table encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.


In a preferred embodiment, the change in biological activity is a decrease in biological activity.


In another preferred embodiment, the biological activity is an enzyme activity, such as where the enzyme is one selected from the group kinase, protease, peptidase, phosphodiesterase, phosphatase, dehydrogenase, reductase, carboxylase. transferase, deacetylase and polymerase.


Assays for these enzymes are available, such as for phosphodiesterases (the most pharmacologically relevant phosphodiesterases are those that hydrolyze cyclic nucleotides (see, for example, cAMP and cGMP assays available from Perkin-Elmer, as well as Estrade et al., Eur. J. Pharmacol. 352:2-3, 157-163 (1998)).


Protein phosphatases remove phosphate residues from proteins. Most tests of their activity use the same assays as for protein kinases. A non-radioactive phosphatase assay system is available from Promega Biotech.


The therapeutically most relevant dehydrogenases oxidize or reduce small molecular weight metabolites, esp. steroid hormones, or that generally use or generate NAD or NADP (see: Haeseleer et al., J. Biol. Chem., 273:21790-21799 (1998)). A commercial assay is available from Cayman Chemical (at www.caymanchem.com).


Gamma-carboxylases are important enzymes in the blood coagulation process. The main assay protocols use synthetic peptides (see: Ulrich et al., J. Biol. Chem., 263:9697-9702 (1988); Begley et al., J. Biol. Chem., 275:36245-36249 (2000)).


In highly preferred embodiments, the kinase is one of a protein kinase, a serine or threonine kinase, or a receptor tyrosine protein kinase. Where the polypeptide encoded by a gene of the invention is a protein kinase, especially involving tyrosine kinase, various assays for activity are available. Protein kinases add phosphate groups to serine, threonine or tyrosine residues on proteins, most commonly measured with phospho-serine, threonine, or tyrosine-specific antibodies, or generation of radiolabeled substrate, or consumption of ATP, or phosphorylation of (synthetic) small peptides, or measuring downstream enzyme activity and gene transcription. Such assays are commercially available. (See, for example, the tyrosine kinase assay from Roche Molecular Biochemicals). Assays for serine/threonine kinases are also available at Chromagen.com, Upstate Biotechnology, Inc. (Lake Placid, N.Y., and at upstatebiotech.com) and from Applied BioSystems (Foster City, Calif. (home.appliedbiosystems.com)).


In other specific embodiments, the protease is a serine protease, cysteine protease or aspartic acid protease, or the transferase is a methyltransferase, preferably a cytosine methyltransferase or an adenine methyltransferase, or the deacetylase is a histone deacetylase, or the carboxylase is a γ-carboxylase, or the peptidase is a zinc peptidase, or the polymerase is a DNA polymerase or an RNA polymerase.


Proteases degrade proteins, un-specifically or at specific sites. Almost all pharmacologically relevant ones have very narrowly defined specific substrates, and their activity is most often measured by directly measuring cleavage product or generation of (fluorescent) light after cleavage of synthetic substrates. Assays are available for serine proteases (Calbiochem, Palo Alto, Calif., and see Berdichevsky et al., J. Virol. Methods, 107:245-255 (2003), for systeine proteases (See: Schulz et al., Mol. Pathol., 51:222-24 (1998) and Seizer et al., PNAS, 96:11015-11022 (1999)), for aspartic acid proteases (Geno Tech, Inc. at www.genotech.com) and for zinc peptidases (see Evans et al., J. Biol. Chem., 278:23180-23186 (2003)).


Both (regulatory) DNA-methylases and (biosynthetic) protein methylases that are drug targets. (See: Jonassen and Clarke, J. Biol. Chem., 275:12381-12387 (2000); Jackson et al., Nature, 416:556-560 (2002)).


Most HDAC (histone deacetylase) assays use colorimetric or fluorometric (synthetic) substrates. Standard assays are for binding, especially molecular size changes, blocking a specific site, and effects on transcription or downstream reactions (if DNA or RNA is the direct target of a drug). A commercial assay is available from Vinci Biochem (at www.vincibiochem.it).


In another specific embodiment, the biological activity is a membrane transport activity, preferably wherein the polypeptide is a cation channel protein, an anion channel protein, a gated-ion channel protein or an ABC transporter protein. Drug effects on the activity of transporter and channel proteins are screened by measuring increase or decrease of the ((radio-)labeled) transported entity inside or outside the cell, in cell-based assays, ATP consumption (in the case of ATPases), or changes in cell membrane potential. Assays employing such proteins are available, such as for ABC transporter (see: Marcil et al., Lancet, 354:1341-46 (1999) and for ion channels (from Evotec OAI, at www.evotecoai.com and from PharmaLinks, at www.pharmalinks.org/research/cellsignalling).


In one embodiment, the polypeptide is an integrin (the signal transduction pathways elicited by the integrins are slow and not very well characterized, hence most assays are either just binding assays or measure downstream biological phenomena (such as migration, invasion, etc.) (See: Ganta et al., Endocrinology, 138:3606-3612 (1997); Sim et al., J. Biomed. Mater. Research, 68A:352-359 (2004); and Weinreb et al., Anal. Biochem., 306:305-313 (2002)), or a Cytochrome P450 enzyme (almost all cytochrome assays require knowledge of what the substrate is and measure conversion of substrate (free or (radio-)labeled) or generation of product; useful C14-labeled substrates are available from Amersham Biosciences at wwwl.amershambiosciences.com), or a nuclear hormone receptor (Assays available from Discoverx, Fremont, Calif., such as an estrogen assay; also see Rosen et al., Curr. Opin. Drug. Discov. Devel., 6:224-30 (2003)).


In one preferred embodiment, the biological activity is a receptor activity, preferably where the receptor is a G-protein-coupled receptor (GPCR).


GPCRs are transmembrane proteins that wind 7 times back and forth through a cell's plasma membrane with a ligand binding site located on the outside of the membrane surface of the cell and the effector site being present inside the cell. These receptors bind GDP and GTP. In response to ligand binding, GPCRs activate signal transduction pathways which induce a number of assayable physiological changes, e.g., an increase in intracellular calcium levels, cyclic-AMP, inositol phosphate turnover, and downstream gene transcription (directly or via reporter-assays) along with other translocation assays available for measuring GPCR activation when the polypeptide encoded by a gene of the invention is a GPCR. Thus, such proteins work through a second messenger. The result is activation of CREB, a transcription factor that stimulates the production of gene products. One useful assay is the so-called BRET2/arrestin assay, useful in screening for compounds that interact with GPCRs. (See: Bertrand et al, J. Recept. Signal Transduct Res., 22:533-41 (February-November 2002)). In addition, numerous assays are commercially available, such as the Transfluor Assay, available from Norak Biosciences, Inc. (www.norakbio.com) or ArrayScan and KineticScan, both from Cellomics, or assays from CyBio (Jena, Germany).


Assays useful with the invention are usually set up to screen for agonists or antagonists after adding ligand, but effects on most of these parameters can be measured whether or not the ligand for the receptor is known. Such assays may involve radioligand-binding assays. Activation of the majority of GPCRs by agonists leads to the interaction of beta-arrestin (a protein that is involved in receptor desensitization and sequestration) with the receptor, which is measurable by fluorescence energy transfer


The disclosure of all journal articles, or other publications, referred to herein are hereby incorporated by reference in their entirety.


In one embodiment, the polypeptide is in a solution or suspension and contact with the test compound is by direct contact between the test compound and the protein molecule. Alternatively, the polypeptide may be in a cell and the test compound may have to diffuse into the cell in order to contact the polypeptide. In an alternative embodiment, the test compound may be contacted with a cell that contains or expresses the polypeptide but the test compound may have no direct contact with the polypeptide. In stead, the test compound may act to induce production and/or activity of a different compound, such as an intracellular second messenger that serves to contact the polypeptide and modulate or change the biological activity of this polypeptide.


In accordance with the foregoing, the method of the present invention includes cancer modulating agents that are themselves either polypeptides, or small chemical entities, that affect the cancerous process, including initiation, suppression or facilitation of tumor growth, either in vivo or ex vivo. Such agents may also be antibodies that react with one or more polypeptides encoded by genes as disclosed herein, preferably polypeptides comprising any one of the amino acid sequences of SEQ ID NO: 806-854.


Because the genes disclosed herein are over-expressed and relate to the cancerous condition of a cell, successful anti-neoplastic activity will commonly be exhibited by agents that reduce the expression of said genes as identified in Table 1. In one embodiment thereof, the change in expression is a decrease in copy number of the gene or genes under study. In accordance therewith, said change in gene copy number is conveniently determined by detecting a change in expression of messenger RNA encoded by said gene sequence. In another preferred embodiment, expression is determined for more than one such gene, such as 2, 5, 10 or more of the genes.


Other methods useful in measuring a change in expression of the genes disclosed herein include measuring a change in the amount or rate of synthesis of a polypeptide encoded by said gene, preferably a decrease in synthesis of said polypeptide. Most preferably, the polypeptide comprises an amino acid sequence highly homologous to a sequence for genes as identified in Table 1 (SEQ ID NO: 1-923).


The methods of the invention can thus be utilized to identify anti-neoplastic agents useful in treatment of cancerous conditions. Such activity can be further modified by first identifying such an agent using an assay as already described and further contacting such agent with a cancerous cell, followed by monitoring of the status of said cell, or cells. A change in status indicative of successful anti-neoplastic activity may include a decrease in the rate of replication of the cancerous cell(s), a decrease in the total number of progeny cells that can be produced by said cancerous cell(s), or a decrease in the number of times said cancerous cell(s) can replicate, or the death of said cancerous cell(s).


Anti-neoplastic agents may also be identified using recombinant cells suitably engineered to contain and express the cancer-related genes disclosed herein. In one such embodiment, a recombinant cell is formed using standard technology and then utilized in the assays disclosed herein. Methods of forming such recombinant cells are well known in the literature. See, for example, Sambrook, et al., Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor, N.Y., (1989), Wu et al, Methods in Gene Biotechnology (CRC Press, New York, N.Y., 1997), and Recombinant Gene Expression Protocols, in Methods in Molecular Biology, Vol. 62, (Tuan, ed., Humana Press, Totowa, N.J., 1997), the disclosures of which are hereby incorporated by reference.


The present invention also relates to a method for detecting the cancerous status of a cell, comprising detecting elevated copy number and/or expression in said cell of at least one gene that maps to the chromosomal region of interest as identified in Table 1 (SEQ ID NO: 1-923). Such elevated expression may be readily monitored by comparison to that of otherwise normal cells having the same genes. Elevated expression of these genes is indicative of the cancerous state. This includes a gene corresponding to a polynucleotide that comprises a nucleotide sequence as identified in Table 1 (SEQ ID NO: 1-923). Such elevated expression, including increased copy number, may be the expression of more than one such gene.


The present invention also relates to a method for detecting a cancer-linked gene comprising the steps of contacting a compound identified as having gene modulating activity for a gene corresponding to a polynucleotide that comprises a nucleotide sequence as identified in Table 1 (SEQ ID NO: 1-923) with a cell expressing a test gene and detecting modulation, such as decreased activity, of such test gene relative to when said compound is not present thereby identifying said test gene as a cancer-related gene. In preferred embodiments, the gene determined by said method is an oncogene, or cancer facilitating gene.


In another embodiment, there is provided a method for treating cancer comprising contacting a cancerous cell with an agent first identified as having gene modulating activity using any of the assay methods disclosed according to the invention and in an amount effective to reduce the cancerous activity of said cell. In a preferred embodiment, the cancerous cell is contacted in vivo. In other preferred embodiments, said reduction in cancerous activity is a decrease in the rate of proliferation of said cancerous cell, or said reduction in cancerous activity is the death of said cancerous cell.


The present invention further relates to a method for treating cancer comprising contacting a cancerous cell with an agent having activity against an expression product encoded by a gene corresponding to a polynucleotide comprising a nucleotide sequence as identified in Table 1 (SEQ ID NO: 1-923) where the product is a polypeptide, most preferably one comprising an amino acid sequence as identified in Table 1 (SEQ ID NO: 806-854). In a preferred embodiment, said cancerous cell is contacted in vivo. In another preferred embodiment, the agent is an antibody.


As noted, the genes useful in the assay methods include genes mapping within chromosomal regions of interest and genes as identified in Table 1 (SEQ ID NO: 1-923), or a gene that encodes the same RNA, such as the same messenger RNA, whose corresponding cDNA is one of the sequences as identified in Table 1 (SEQ ID NO: 1-923). The genes useful in the methods of the invention further include genes encoding RNAs whose corresponding cDNA is at least 90% identical to a sequence as identified in Table 1 (SEQ ID NO: 1-923), preferably at least about 95% identical to such a sequence, more preferably at least about 98% identical to such sequence and most preferably one comprising that sequence are specifically contemplated by all of the methods of the present invention.


In addition, sequences encoding the same proteins (SEQ ID NO: 806-854) as any of these sequences, regardless of the percent identity of such sequences, are also specifically contemplated by the invention.


The sequences disclosed herein may be genomic in nature and thus represent the sequence of an actual gene, such as a human gene, or may be a cDNA sequence derived from a messenger RNA (mRNA) and thus represent contiguous exonic sequences derived from a corresponding genomic sequence or they may be wholly synthetic in origin for purposes of testing. As described in the Example, the expression of these cancer-related genes is determined from the relative expression levels of the RNA complement of a cancerous cell relative to a normal (i.e., non-cancerous) cell. Because of the processing that may take place in transforming the initial RNA transcript into the final mRNA, the sequences disclosed herein may represent less than the full genomic sequence. They may also represent sequences derived from ribosomal and transfer RNAs. Consequently, the genes present in the cell (and representing the genomic sequences) and the sequences disclosed herein, which are mostly cDNA sequences, may be identical or may be such that the cDNAs contain less than the full genomic sequence. Such genes and cDNA sequences are still considered corresponding sequences because they both encode similar RNA sequences. Thus, by way of non-limiting example only, a gene that encodes an RNA transcript, which is then processed into a shorter mRNA, is deemed to encode both such RNAs and therefore encodes an RNA complementary to (using the usual Watson-Crick complementarity rules), or that would otherwise be encoded by, a cDNA (for example, a sequence as disclosed herein). Thus, the sequences disclosed herein correspond to genes contained in the cancerous or normal cells used to determine relative levels of expression because they represent the same sequences or are complementary to RNAs encoded by these genes. Such genes also include different alleles and splice variants that may occur in the cells used in the methods of the invention.


The genes of the invention “correspond to” a polynucleotide having a sequence as identified in Table 1 (SEQ ID NO: 1-923) if the gene encodes an RNA (processed or unprocessed, including naturally occurring splice variants and alleles) that is at least 90% identical, preferably at least 95% identical, most preferably at least 98% identical to, and especially identical to, an RNA that would be encoded by, or be complementary to, such as by hybridization with, a polynucleotide having the indicated sequence. In addition, genes including sequences at least 90% identical to a sequence as identified in Table 1 (SEQ ID NO: 1-923), preferably at least about 95% identical to such a sequence, more preferably at least about 98% identical to such sequence and most preferably comprising such sequence are specifically contemplated by all of the methods of the present invention as being genes that correspond to these sequences. In addition, sequences encoding the same proteins as any of these sequences, regardless of the percent identity of such sequences, are also specifically contemplated by any of the methods of the present invention that rely on any or all of said sequences, regardless of how they are otherwise described or limited. Thus, any such sequences are available for use in carrying out any of the methods disclosed according to the invention. Such sequences also include any open reading frames, as defined herein, present within any of the sequences as identified in Table 1 (SEQ ID NO: 1-805 and 855-923).


Further in accordance with the present invention, the term “percent identity” or “percent identical,” when referring to a sequence, means that a sequence is compared to a claimed or described sequence after alignment of the sequence to be compared (the “Compared Sequence”) with the described or claimed sequence (the “Reference Sequence”). The Percent Identity is then determined according to the following formula:

Percent Identity=100[1−(C/R)]

wherein C is the number of differences between the Reference Sequence and the Compared Sequence over the length of alignment between the Reference Sequence and the Compared Sequence wherein (i) each base or amino acid in the Reference Sequence that does not have a corresponding aligned base or amino acid in the Compared Sequence and (ii) each gap in the Reference Sequence and (iii) each aligned base or amino acid in the Reference Sequence that is different from an aligned base or amino acid in the Compared Sequence, constitutes a difference; and R is the number of bases or amino acids in the Reference Sequence over the length of the alignment with the Compared Sequence with any gap created in the Reference Sequence also being counted as a base or amino acid.


If an alignment exists between the Compared Sequence and the Reference Sequence for which the percent identity as calculated above is about equal to or greater than a specified minimum Percent Identity then the Compared Sequence has the specified minimum percent identity to the Reference Sequence even though alignments may exist in which the hereinabove calculated Percent Identity is less than the specified Percent Identity.


As used herein, the terms “portion,” “segment,” and “fragment,” when used in relation to polypeptides, refer to a continuous sequence of residues, such as amino acid residues, which sequence forms a subset of a larger sequence. For example, if a polypeptide were subjected to treatment with any of the common endopeptidases, such as trypsin or chymotrypsin, the oligopeptides resulting from such treatment would represent portions, segments or fragments of the starting polypeptide. When used in relation to a polynucleotide, such terms refer to the products produced by treatment of said polynucleotides with any of the common endonucleases, or any stretch of polynucleotides that could be synthetically synthesized.


As used herein, the term “DNA segment” or “DNA sequence” refers to a DNA polymer, in the form of a separate fragment or as a component of a larger DNA construct, which has been derived from DNA, and may include both single stranded and duplex sequences. Such segments are provided in the form of an open reading frame uninterrupted by internal non-translated sequences, or introns, which are typically present in eukaryotic genes.


The term “coding region” refers to that portion of a gene which either naturally or normally codes for the expression product of that gene in its natural genomic environment, i.e., the region coding in vivo for the native expression product of the gene.


The term “nucleotide sequence” refers to a heteropolymer of deoxyribonucleotides. Generally, DNA segments encoding the proteins provided by this invention are assembled from cDNA fragments and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon.


The term “expression product” means that polypeptide or protein that is the natural translation product of the gene and any nucleic acid sequence coding equivalents resulting from genetic code degeneracy and thus coding for the same amino acid(s).


The term “fragment,” when referring to a coding sequence, means a portion of DNA comprising less than the complete coding region whose expression product retains essentially the same biological function or activity as the expression product of the complete coding region.


The present invention also finds use as a means of diagnosing the presence of cancer in a patient, as where a sample of cancerous tissues or cells, or tissues or cells suspected of being cancerous. For such purposes, and in accordance with the disclosure elsewhere herein, such diagnosis is based on the detection of elevated expression or amplification, such as elevated copy number, of one or more of the genes identified according to the invention. Such elevated expression can be determined by any of the means described herein.


In one such embodiment, the elevated expression, as compared to normal cells and/or tissues of the same organ, is determined by measuring the relative rates of transcription of RNA, such as by production of corresponding cDNAs and then analyzing the resulting DNA using probes developed from the gene sequences as identified in Table 1. Thus, the levels of cDNA produced by use of reverse transcriptase with the full RNA complement of a cell suspected of being cancerous produces a corresponding amount of cDNA that can then be amplified using polymerase chain reaction, or some other means, such as rolling circle amplification, to determine the relative levels of resulting cDNA and, thereby, the relative levels of gene expression.


For RNA analysis, the latter may be isolated from samples in a variety of ways, including lysis and denaturation with a phenolic solution containing a chaotropic agent (e.g., triazol) followed by isopropanol precipitation, ethanol wash, and resuspension in aqueous solution; or lysis and denaturation followed by isolation on solid support, such as a Qiagen resin and reconstitution in aqueous solution; or lysis and denaturation in non-phenolic, aqueous solutions followed by enzymatic conversion of RNA to DNA template copies. Steady state RNA levels for a given type of cell or tissue may have to be ascertained prior to employment of the methods of the invention but such is well within the skill of those in the art and will not be further described in detail herein.


Alternatively, increased expression, such as increased copy number, may be determined for the genes present in a cancerous cell, or a cell suspected of being cancerous, by using the nucleotides sequences as identified in Table 1 as a means of generating probes for the DNAs present in the cells to be examined. Thus, the DNA of such cells may be extracted and probed using the sequences disclosed herein for the presence in the genomes of such cells of increased amounts of one or more of the genes of the invention. For example, where a cancer-related, or cancer-linked, gene as disclosed herein is found to be present in multiple copies within the genome of a cell, even where it may not be actively being over-expressed at the time of such determination, this may be indicative of at least a disposition toward developing cancer at a subsequent time.


In accordance with the foregoing, the presence of such multiple copies of a gene, or genes, as disclosed herein may be determined using northern or southern blotting and employing the sequences as identified in Table 1 to develop probes for this purpose. Such probes may be composed of DNA or RNA and may advantageously be comprised of a contiguous stretch of nucleotide residues matching, or complementary to, a sequence as identified in Table 1. Such probes will most usefully comprise a contiguous stretch of at least 15, preferably at least 30, more preferably at least 50, most preferably at least 80, and especially at least 100, even 200 residues, derived from one or more of the sequences as identified in Table 1. Thus, where a single probe binds multiple times to the genome of a sample of cells that are cancerous, or are suspected of being cancerous, or predisposed to become cancerous, whereas binding of the same probe to a similar amount of DNA derived from the genome of otherwise non-cancerous cells of the same organ or tissue results in observably less binding, this is indicative of the presence of multiple copies of a gene comprising, or corresponding to, the sequence as identified in Table 1 from which the probe sequenced was derived.


Increased expression may also be determined using agents that selectively bind to, and thereby detect, the presence of expression products of the genes disclosed herein. For example, an antibody, possibly a suitably labeled antibody, such as where the antibody is bound to a fluorescent or radiolabel, may be generated against one of the polypeptides comprising a sequence as identified in Table 1 (serial number 1-229 (breast), 230-440 (colon), 441-656 (lung) and 657-805 (prostate); for polypeptide SEQ ID NOs, see Table 1, serial number 806-923 (transcript or protein)), and said antibody will then react with, binding either selectively or specifically, to a polypeptide encoded by one of the genes that corresponds to a sequence disclosed herein. Such antibody binding, especially relative extent of such binding in samples derived from suspected cancerous, as opposed to otherwise non-cancerous, cells and tissues, can then be used as a measure of the extent of expression, or over-expression, of the cancer-related genes identified herein. Thus, the genes identified herein as being over-expressed in cancerous cells and tissues may be over-expressed due to increased copy number, or due to over-transcription, such as where the over-expression is due to over-production of a transcription factor that activates the gene and leads to repeated binding of RNA polymerase, thereby generating large than normal amounts of RNA transcripts, which are subsequently translated into polypeptides, such as the polypeptides comprising amino acid sequences as identified in table 1)SEQ ID NO: 1-923). Such analysis provides an additional means of ascertaining the expression of the genes identified according to the invention and thereby determining the presence of a cancerous state in a sample derived from a patient to be tested, of the predisposition to develop cancer at a subsequent time in said patient.


In employing the methods of the invention, it should be borne in mind that gene expression indicative of a cancerous state need not be characteristic of every cell found to be cancerous. Thus, the methods disclosed herein are useful for detecting the presence of a cancerous condition within a tissue where less than all cells exhibit the complete pattern of over-expression. For example, a set of selected genes, comprising sequences homologous under stringent conditions, or at least 90%, preferably 95%, identical to at least one of the sequences as identified in Table 1, may be found, using appropriate probes, either DNA or RNA, to be present in as little as 60% of cells derived from a sample of tumorous, or malignant, tissue while being absent from as much as 60% of cells derived from corresponding non-cancerous, or otherwise normal, tissue (and thus being present in as much as 40% of such normal tissue cells). In a preferred embodiment, such gene pattern is found to be present in at least 70% of cells drawn from a cancerous tissue and absent from at least 70% of a corresponding normal, non-cancerous, tissue sample. In an especially preferred embodiment, such gene pattern is found to be present in at least 80% of cells drawn from a cancerous tissue and absent from at least 80% of a corresponding normal, non-cancerous, tissue sample. In a most preferred embodiment, such gene pattern is found to be present in at least 90% of cells drawn from a cancerous tissue and absent from at least 90% of a corresponding normal, non-cancerous, tissue sample. In an additional embodiment, such gene pattern is found to be present in at least 100% of cells drawn from a cancerous tissue and absent from at least 100% of a corresponding normal, non-cancerous, tissue sample, although the latter embodiment may represent a rare occurrence.


In an additional aspect, the present invention relates to a method for determining a cancer initiating or facilitating gene comprising contacting a cell expressing a test gene (i.e., a gene whose status as a cancer initiating or facilitating gene is to be determined) with an agent that decreases the expression of a gene that encodes an RNA at least 90%, preferably 95%, identical to an RNA encoded by (i.e., a gene corresponding to) a polynucleotide comprising, or having, a sequence selected from the group consisting as identified in Table 1 and detecting a decrease in expression of said test gene compared to when said agent is not present, thereby identifying said test gene as being a cancer initiating or facilitating gene. Such genes may, of course, be oncogenes and said decrease in expression may be due to a decrease in copy number of said gene in said cell or a cell derived from said cell, such as where copy number is reduced in the cells formed by replication of such cells.


Thus, some or all of the genes disclosed herein as corresponding to as identified in Table 1 are found to play a direct role in the initiation or progression of cancer or even other diseases and disease processes. Because changes in expression of these genes (up-regulation) are linked to the disease state (i.e. cancer), the change in expression may contribute to the initiation or progression of the disease. For example, if a gene that is up-regulated is an oncogene such a gene provides for a means of screening for small molecule therapeutics beyond screens based upon expression output alone. For example, genes that display up-regulation in cancer and whose elevated expression contributes to initiation or progression of disease represent targets in screens for small molecules that inhibit or block their function. Examples include, but are not be limited to, kinase inhibition, cellular proliferation, substrate analogs that block the active site of protein targets, etc.


It should be noted that there are a variety of different contexts in which genes have been evaluated as being involved in the cancerous process. Thus, some genes may be oncogenes and encode proteins that are directly involved in the cancerous process and thereby promote the occurrence of cancer in an animal. Other genes may simply be involved either directly or indirectly in the cancerous process or condition and may serve in an ancillary capacity with respect to the cancerous state. All such types of genes are deemed with those to be determined in accordance with the invention as disclosed herein. Thus, the gene determined by said method of the invention may be an oncogene, or the gene determined by said method may be a cancer facilitating gene, the latter including a gene that directly or indirectly affects the cancerous process, either in the promotion of a cancerous condition or in facilitating the progress of cancerous growth or otherwise modulating the growth of cancer cells, either in vivo or ex vivo. Such genes may work indirectly where their expression alters the activity of some other gene or gene expression product that is itself directly involved in initiating or facilitating the progress of a cancerous condition. For example, a gene that encodes a polypeptide, either wild or mutant in type, which polypeptide acts to suppress of tumor suppressor gene, or its expression product, will thereby act indirectly to promote tumor growth.


In accordance with the foregoing, the method of the present invention includes cancer modulating agents that are themselves either polypeptides, or small chemical entities, that affect the cancerous process, including initiation, suppression or facilitation of tumor growth, either in vivo or ex vivo. Such agents may also be antibodies that react with one or more of the polypeptides as identified in Table 1 ((SEQ ID NO: 806-923 (transcript or protein)).


In keeping with the disclosure herein, the present invention also relates to a method for treating cancer comprising contacting a cancerous cell with an agent having activity against an expression product encoded by a gene mapping within regions of chromosomal interest or, alternatively, a gene corresponding to a polynucleotide that comprises a nucleotide sequence as identified in Table 1, such as where such expression product is one the polypeptides as identified in Table 1.


The method of the present invention includes embodiments of the above-recited method wherein said cancer cell is contacted in vivo as well as ex vivo, preferably wherein said agent comprises a portion, or is part of an overall molecular structure, having affinity for said expression product. In one such embodiment, said portion having affinity for said expression product is an antibody.


In one embodiment of the present invention, a chemical agent, such as a protein or other polypeptide, is joined to an agent, such as an antibody, having affinity for an expression product of a cancerous cell, such as a polypeptide or protein encoded by a gene related to the cancerous process, especially a gene sequence corresponding to one of the cDNA sequences as identified in Table 1. In a specific embodiment, said expression product acts as a therapeutic target for the affinity portion of said anticancer agent and where, after binding of the affinity portion of such agent to the expression product, the anti-cancer portion of said agent acts against said expression product so as to neutralize its effects in initiating, facilitating or promoting tumor formation and/or growth. In a separate embodiment of the present invention, binding of the agent to said expression product may, without more, have the effect of deterring cancer promotion, facilitation or growth, especially where the presence of said expression product is related, either intimately or only in an ancillary manner, to the development and growth of a tumor. Thus, where the presence of said expression product is essential to tumor initiation and/or growth, binding of said agent to said expression product will have the effect of negating said tumor promoting activity. In one such embodiment, said agent is an apoptosis-inducing agent that induces cell suicide, thereby killing the cancer cell and halting tumor growth.


Many cancers contain chromosomal rearrangements, which typically represent translocations, amplifications, or deletions of specific regions of genomic DNA. A recurrent chromosomal rearrangement that is associated with a specific stage and type of cancer always affects a gene (or possibly genes) that play a direct and critical role in the initiation or progression of the disease. Many of the known oncogenes or tumor suppressor genes that play direct roles in cancer have either been initially identified based upon their positional cloning from a recurrent chromosomal rearrangement or have been demonstrated to fall within a rearrangement subsequent to their cloning by other methods. In all cases, such genes display amplification at both the level of DNA copy number and at the level of transcriptional expression at the mRNA level.


The present method also relates to a method for determining functionally related genes comprising contacting one or more gene sequences corresponding to the cDNAs as identified in Table 1 with an agent that modulates expression of more than one gene in such group and thereby determining a subset of genes of said group.


In accordance with the present invention, said functionally related genes are genes modulating the same metabolic pathway or said genes are genes encoding functionally related polypeptides. In one such embodiment, said genes are genes whose expression is modulated by the same transcriptional activator or enhancer sequence, especially where said transcriptional activator or enhancer increases, or otherwise modulates, the activity of a gene corresponding to a cDNA as identified in Table 1.


The present invention also relates to a process that comprises a method for producing a product comprising identifying an agent according to one of the disclosed methods for identifying such an agent (i.e., the therapeutic agents identified according to the assay procedures disclosed herein) wherein said product is the data collected with respect to said agent as a result of said identification process, or assay, and wherein said data is sufficient to convey the chemical character and/or structure and/or properties of said agent. For example, the present invention specifically contemplates a situation whereby a user of an assay of the invention may use the assay to screen for compounds having the desired enzyme modulating activity and, having identified the compound, then conveys that information (i.e., information as to structure, dosage, etc) to another user who then utilizes the information to reproduce the agent and administer it for therapeutic or research purposes according to the invention. For example, the user of the assay (user 1) may screen a number of test compounds without knowing the structure or identity of the compounds (such as where a number of code numbers are used the first user is simply given samples labeled with said code numbers) and, after performing the screening process, using one or more assay processes of the present invention, then imparts to a second user (user 2), verbally or in writing or some equivalent fashion, sufficient. information to identify the compounds having a particular modulating activity (for example, the code number with the corresponding results). This transmission of information from user 1 to user 2 is specifically contemplated by the present invention.


In accordance with the foregoing, the present invention relates to a method for producing test data with respect to the anti-neoplastic activity of a compound comprising:


(a) contacting a compound with a cell that expresses at least one gene corresponding to a polynucleotide comprising a nucleotide sequence of serial number 1-229 (breast), 230-440 (colon), 441-656 (lung) and 657-805 (prostate) of Table 1 or encoding a polypeptide or transcript of SEQ ID NO:


806-923 and under conditions promoting expression of said gene;


(b) detecting a change in expression of said gene compared to expression when said compound is not present; and


(c) producing test data with respect to the gene modulating activity of said compound based on a change in the expression of the determined gene, or genes, whose expression is otherwise elevated in a non-cancerous cell over that in a cancerous cell and a decrease in the expression of the determined gene, or genes whose expression is otherwise increased in a cancerous cell over that in a non-cancerous cell indicating anti-neoplastic activity.


In another embodiment, the present invention provides a method for monitoring the progress of a cancer treatment, such as where the methods of the invention permit a determination that a given course of cancer therapy is or is not proving effective because of an increased or decreased expression of a gene, or genes, disclosed herein. For example, where there is an increased copy number of one or more of the genes as identified in Table 1 (SEQ ID NO: 1-805), monitoring of such genes can predict success or failure of a course of therapy, such as chemotherapy, or predict the likelihood of a relapse based on elevated activity or expression of one or more of these genes following such course of therapy.


In accordance with the foregoing, the present invention contemplates a method for determining the progress of a treatment for cancer in a patient afflicted with cancer, following commencement of a cancer treatment on said patient, comprising:


(a) determining in said patient a change in expression of one or more genes corresponding to a polynucleotide comprising a nucleotide sequence of serial number 1-229 (breast), 230-440 (colon), 441-656 (lung) and 657-805 (prostate) of Table 1 or encoding a polypeptide or transcript of serial number 806-923 of table 1) which include any of SEQ ID NO: 1-923) and under conditions promoting expression of said one or more genes; and


(b) detecting a change in expression of said gene compared to expression of said one or more determined genes prior to commencement of said cancer treatment;


thereby determining the progress of said treatment.


In a preferred embodiment, the detected change in expression is a decrease in expression. In another preferred embodiment, the cancer treatment is treatment with a chemotherapeutic agent, especially an agent that modulates, preferably decreases, expression of a gene identified herein, such as where said agent was first identified as having anti-neoplastic activity using a method of the invention. Thus, in accordance with this aspect of the present invention, a patient, or even a research animal, such as a mouse, rat, rabbit or primate, afflicted with cancer, including a cancer induced for research purposes, is introduced to a cancer treatment regimen, such as administration of an anti-cancer agent, including one first identified as having anti-neoplastic activity by one or more of the screening methods disclosed herein. The progress and success or failure of such treatment is subsequently ascertained by determining the subsequent expression of one or more, preferably at least 3, or 5, or 10, of the genes identified herein, or that encodes a transcript or polypeptide disclosed herein (see Table 1) following said treatment. In a preferred embodiment, a treatment that reduces said expression is deemed advantageous and may then be the basis for continuing said treatment. The methods of the invention thereby provide a means of continually monitoring the success of the treatment and evaluating both the need, and desirability, of continuing said treatment. In addition, more than one said treatment may be administered simultaneously without diminishing the value of the methods of the invention in determining the overall success of such combined treatment. Thus, more than one said anti-neoplastic agent may be administered to the same patient and overall effectiveness ascertained by the recited methods.


In accordance with the foregoing, the present invention also contemplates a method for determining the likelihood of survival of a patient afflicted with cancer, following commencement of a cancer treatment on said patient, comprising:


(a) determining in said patient a change in expression of one or more genes corresponding to a polynucleotide comprising a nucleotide sequence of serial number 1-229 (breast), 230-440 (colon), 441-656 (lung) and 657-805 (prostate) of Table 1 or encoding a polypeptide or transcript of serial number 806-923 of Table 1 and under conditions promoting expression of said one or more genes; and


(b) detecting a change in expression of said gene compared to expression of said one or more determined genes prior to commencement of said cancer treatment;


thereby determining the likelihood of survival of said treatment.


In a preferred embodiment, the detected change in expression is a decrease in expression and said determined gene, or genes, may include 2, 3, 5, 10 or more of the genes described herein. Thus, the methods of the invention may be utilized as a means for compiling cancer survival statistics following one or more, possibly combined, treatments for cancer as in keeping with the other methods disclosed herein.


The genes identified herein also offer themselves as pharmacodynamic markers (or as pharmacogenetic and/or surrogate markers), such as for patient profiling prior to clinical trials and/or targeted therapies, including combination treatments, resulting from the identification of these genes as valid gene targets for chemotherapy based on the screening procedures of the invention. In one embodiment thereof, the likelihood of success of a cancer treatment with a selected chemotherapeutic agent may be based on the fact that such agent has been determined to have expression modulating activity with one or more genes identified herein, especially where said genes have been identified as showing elevated expression levels in samples from a prospective patient afflicted with cancer. Methods described elsewhere herein for determining cancerous status of a cell may find ready use in such evaluations.


It should be cautioned that, in carrying out the procedures of the present invention as disclosed herein, any reference to particular buffers, media, reagents, cells, culture conditions and the like are not intended to be limiting, but are to be read so as to include all related materials that one of ordinary skill in the art would recognize as being of interest or value in the particular context in which that discussion is presented. For example, it is often possible to substitute one buffer system or culture medium for another and still achieve similar, if not identical, results. Those of skill in the art will have sufficient knowledge of such systems and methodologies so as to be able, without undue experimentation, to make such substitutions as will optimally serve their purposes in using the methods and procedures disclosed herein.


The present invention will now be further described by way of the following non-limiting example. In applying the disclosure of the example, it should be kept clearly in mind that other and different embodiments of the methods disclosed according to the present invention will no doubt suggest themselves to those of skill in the relevant art.







EXAMPLE

Cancerous cells that over-express one or more of the genes selected from those that correspond to genes as identified in Table 1 (serial number 1-229 (breast), 230-440 (colon), 441-656 (lung) and 657-805 (prostate); serial number 806-923 (transcript or protein), or SEQ ID NO: 1-805 and 855-923) are grown to a density of 105 cells/cm2 in Leibovitz's L-15 medium supplemented with 2 mM L-glutamine (90%) and 10% fetal bovine serum. The cells are collected after treatment with 0.25% trypsin, 0.02% EDTA at 37° C. for 2 to 5 minutes. The trypsinized cells are then diluted with 30 ml growth medium and plated at a density of 50,000 cells per well in a 96 well plate (200 μl/well). The following day, cells are treated with either compound buffer alone, or compound buffer containing a chemical agent to be tested, for 24 hours. The media is then removed, the cells lysed and the RNA recovered using the RNAeasy reagents and protocol obtained from Qiagen. RNA is quantitated and 10 ng of sample in 1 μl are added to 24 μl of Taqman reaction mix containing 1X PCR buffer, RNAsin, reverse transcriptase, nucleoside triphosphates, amplitaq gold, tween 20, glycerol, bovine serum albumin (BSA) and specific PCR primers and probes for a reference gene (18S RNA) and a test gene (Gene X). Reverse transcription is then carried out at 48° C. for 30 minutes. The sample is then applied to a Perlin Elmer 7700 sequence detector and heat denatured for 10 minutes at 95° C. Amplification is performed through 40 cycles using 15 seconds annealing at 60° C. followed by a 60 second extension at 72° C. and 30 second denaturation at 95° C. Data files are then captured and the data analyzed with the appropriate baseline windows and thresholds.


The quantitative difference between the target and reference genes is then calculated and a relative expression value determined for all of the samples used. This procedure is then repeated for each of the target genes in a given signature, or characteristic, set and the relative expression ratios for each pair of genes is determined (i.e., a ratio of expression is determined for each target gene versus each of the other genes for which expression is measured, where each gene's absolute expression is determined relative to the reference gene for each compound, or chemical agent, to be screened). The samples are then scored and ranked according to the degree of alteration of the expression profile in the treated samples relative to the control. The overall expression of the set of genes relative to the controls, as modulated by one chemical agent relative to another, is also ascertained. Chemical agents having the most effect on a given gene, or set of genes, are considered the most anti-neoplastic.

TABLE 1SerialProtein/No.SEQ IDaccessiontissuep_mchrbandunigeneDescriptionTranscript13AK000490breastprimary1p31.2Hs.133260hypothetical protein FLJ20354210R33352breastprimary1p31.3NULLunknown313AI739473breastprimary1p32.3Hs.7561624-dehydrocholesterol reductase45U63743breastprimary1p34.1Hs.69360kinesin-like 6 (mitotic centromere-associatedkinesin)52U05340breastprimary1p34.2Hs.82906CDC20 cell division cycle 20 homolog (S. cerevisiae)611AA203213breastprimary1p36.33Hs.833interferon-stimulated protein 15 kDa712T16144breastprimary1q21.3NULLunknown81AI053741breastprimary1q22Hs.133294ESTs914AB037776breastprimary1q23.1Hs.38002immunoglobulin superfamily member 9109AA830844breastprimary1q23.2Hs.127310kinase interacting with leukemia-associatedgene (stathmin)117AF326731breastprimary1q23.3Hs.234545cell division cycle associated 1124AB032931breastprimary1q32.1Hs.5199HSPC150 protein similar to ubiquitin-conjugating enzyme138AI380204breastprimary1q32.1Hs.118064similar to rat nuclear ubiquitous casein kinase 2146U30872breastprimary1q32.3Hs.77204centromere protein F 350/400 ka (mitosin)1555U14518breastprimary2p23.3Hs.1594centromere protein A 17 kDa1654AI492879breastprimary2p25.1Hs.75319ribonucleotide reductase M2 polypeptide1756AL045632breastprimary2q33.1Hs.44269hypothetical protein FLJ252111874M86699breastprimary3p21.31Hs.169840TTK protein kinase1977AI962335breastprimary3p24.3Hs.196042ESTs2075AI867102breastprimary3p25.1Hs.56966KIAA0906 protein2171AI751438breastprimary3q12.3Hs.41271Homo sapiens mRNA full length insert cDNAclone EUROIMAGE 19130762272X57527breastprimary3q12.3Hs.114599collagen type VIII alpha 12376W02608breastprimary3q26.1Hs.36830ESTs Moderately similar to zinc finger protein91 (HPF7 HTF10) [Homo sapiens] [H. sapiens]2473AI823992breastprimary3q26.32Hs.122579epithelial cell transforming sequence 2oncogene2578AI087975breastprimary3q28Hs.195225ESTs2682AW001872breastprimary5p13.1Hs.58435FYN binding protein (FYB-120/130)2780BE407516breastprimary5q13.2Hs.23960cyclin B12881U70370breastprimary5q31.1Hs.84136paired-like homeodomain transcription factor 12979AI739117breastprimary5q31.2Hs.73625RAB6 interacting kinesin-like (rabkinesin6)3083D14678breastprimary6p21.32Hs.20830kinesin-like 23185M13436breastprimary7p14.1Hs.727inhibin beta A (activin A activin AB alphapolypeptide)3286AI343467breastprimary7p14.1Hs.28792Homo sapiens cDNA FLJ11041 fis clonePLACE10044053384AK023208breastprimary7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)3489AI285531breastprimary7p15.2Hs.106260sorting nexin 103587AI922323breastprimary7p21.1Hs.91011anterior gradient 2 homolog (Xenepus laevis)3688U61145breastprimary7q36.1Hs.77256enhancer of zeste homolog 2 (Drosophila)3799AA625199breastprimary8NULLHs.352415solute carrier family 39 (zinc transporter)member 438100AI949095breastprimary8NULLHs.67776Homo sapiens clone IMAGE: 5455669 mRNApartial cds3990AI932328breastprimary8p21.1Hs.104741T-LAK cell-originated protein kinase4091AA203476breastprimary8q13.2Hs.252587pituitary tumor-transforming 14192AW043713breastprimary8q13.3Hs.70823sulfatase FP4296BE974098breastprimary8q21.13Hs.2384tumor protein D524398AF091433breastprimary8q22.1Hs.30464cyclin E24495AA046853breastprimary8q24.12Hs.76550mal T-cell differentiation protein 24593AI925583breastprimary8q24.13Hs.222088hypothetical protein MGC52544697AF098865breastprimary8q24.13Hs.71465squalene epoxidase4794AA147884breastprimary8q24.22Hs.9812Homo sapiens cDNA FLJ14388 fis cloneHEMBA100271648103AW007586breastprimary9q34.11Hs.133122zinc finger DHHC domain containing 1249101W25552breastprimary9q34.3Hs.212613hypothetical protein FLJ3677950102AI811865breastprimary9q34.3Hs.274152EST5117AF067656breastprimary10q21.1Hs.42650ZW10 interactor5216AL524035breastprimary10q21.2Hs.334562cell division cycle 2 G1 to S and G2 to M5315AI674163breastprimary10q23.33Hs.14559hypothetical protein FLJ105405421AB018293breastprimary11p15.3Hs.314434KIAA0750 gene product5518AL079372breastprimary11q13.1Hs.23044similar to RIKEN cDNA 2610036L135622D60944breastprimary11q13.4Hs.84700serologically defined colon cancer antigen 285719X14850breastprimary11q23.3Hs.147097H2A histone family member X5820AA704137breastprimary11q23.3Hs.125359Thy-1 cell surface antigen5923U74612breastprimary12p13.33Hs.239forkhead box M16024U82984breastprimary12q13.12Hs.23900Rac GTPase activating protein 16125AI291142breastprimary13q33.3Hs.183874cullin 4A6226L25876breastprimary14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)6327AL080146breastprimary15q21.3Hs.194698cyclin B26428D14657breastprimary15q22.2Hs.81892KIAA0101 gene product6529AA195614breastprimary15q25.3Hs.344037protein regulator of cytokinesis 16631AW003626breastprimary16NULLHs.159154tubulin beta 46732BC003186breastprimary16NULLHs.108196HSPC037 protein6830AI819340breastprimary16p13.3Hs.13561hypothetical protein MGC46926934W92110breastprimary16p13.3Hs.279623selenoprotein × 17035AI953838breastprimary16p13.3Hs.124015hypothetical protein MGC26057136AL520675breastprimary16p13.3Hs.351474hypothetical protein FLJ300027237BE965311breastprimary16p13.3Hs.124915hypothetical protein MGC26017338AI701742breastprimary16p13.3Hs.290943Homo sapiens similar to possible G-proteinreceptor clone MGC: 21993 IMAGE: 4398317mRNA complete cds7433AA904482breastprimary16q12.2Hs.368078ESTs7542AI683036breastprimary17NULLHs.314169KIAA1618 protein7644U81800breastprimary17NULLHs.85838solute carrier family 16 (monocarboxylic acidtransporters) member 37745BE328850breastprimary17q11.2Hs.348504hypothetical protein BC0140727839AW003286breastprimary17q21.31Hs.370428ESTs Moderately similar to TP2A_HUMANDNA topoisomerase II alpha isozyme[H. sapiens]7941AL561834breastprimary17q21.31Hs.156346topoisomerase (DNA) II alpha 170 kDa8048L47276breastprimary17q21.31NULLunknown8149BC001038breastprimary17q22Hs.307036Homo sapiens Similar to epsin 3 cloneMGC: 1006 IMAGE: 3505495 mRNA completecds8240AA424160breastprimary17q23.2Hs.165909ESTs Weakly similar to hypothetical proteinFLJ20489 [Homo sapiens] [H. sapiens]8351BF029215breastprimary17q23.2Hs.103512Homo sapiens cDNA FLJ36569 fis cloneTRACH2010824 highly similar toRibonucleoprotein8443AI675178breastprimary17q24.2Hs.90207hypothetical protein MGC111388550U28386breastprimary17q24.3Hs.159557karyopherin alpha 2 (RAG cohort 1 importinalpha 1)8646AA635844breastprimary17q25.3Hs.109706hematological and neurological expressed 18747K02581breastprimary17q25.3Hs.105097thymidine kinase 1 soluble8852AF017790breastprimary18p11.32Hs.58169highly expressed in cancer rich in leucineheptad repeats8953AA719022breastprimary19q13.43Hs.288549ubiquitin UBF-fl9065D80008breastprimary20p11.21Hs.36232KIAA0186 gene product9163AI990405breastprimary20p11.23Hs.194691retinoic acid induced 39257AA534688breastprimary20q11.1Hs.9329chromosome 20 open reading frame 19366AW003586breastprimary20q11.22Hs.274411SCAN domain containing 19459U73379breastprimary20q13.12Hs.93002ubiquitin-conjugating enzyme E2C9562AI990026breastprimary20q13.12Hs.286ribosomal protein L49667AA207074breastprimary20q13.13Hs.56237breast carcinoma amplified sequence 49760AF041260breastprimary20q13.2Hs.129057breast carcinoma amplified sequence 19861AF011468breastprimary20q13.31Hs.250822serine/threonine kinase 69958AA535819breastprimary20q13.32Hs.83883transmembrane prostate androgen inducedRNA10064X70940breastprimary20q13.33Hs.2642eukaryotic translation elongation factor 1 alpha 210169Y15915breastprimary22q13.1Hs.172928collagen type I alpha 110270AL035081breastprimary22q13.1Hs.250696KDEL (Lys-Asp-Glu-Leu) endoplasmicreticulum protein retention receptor 310368AI381686breastprimary22q13.2Hs.208912hypothetical protein MGC861104106AK000490breastmetastatic1p31.2Hs.133260hypothetical protein FLJ20354105113R33352breastmetastatic1p31.3NULLunknown106116AI739473breastmetastatic1p32.3Hs.7561624-dehydrocholesterol reductase107108U63743breastmetastatic1p34.1Hs.69360kinesin-like 6 (mitotic centromere-associatedkinesin)108105U05340breastmetastatic1p34.2Hs.82906CDC20 cell division cycle 20 homolog (S. cerevisiae)109119AI992172breastmetastatic1p36.13Hs.83551microfibrillar-associated protein 2110114AA203213breastmetastatic1p36.33Hs.833interferon-stimulated protein 15 kDa111115T16144breastmetastatic1q21.3NULLunknown112104AI053741breastmetastatic1q22Hs.133294ESTs113118AB037776breastmetastatic1q23.1Hs.38002immunoglobulin superfamily member 9114112AA830844breastmetastatic1q23.2Hs.127310kinase interacting with leukemia-associatedgene (stathmin)115120R62346breastmetastatic1q23.2NULLunknown116110AF326731breastmetastatic1q23.3Hs.234545cell division cycle associated 1117117AI983896breastmetastatic1q23.3Hs.191187ESTs118121AI798144breastmetastatic1q25.2Hs.209609ESTs119107AI990409breastmetastatic1q32.1Hs.5199HSPC150 protein similar to ubiquitin-conjugating enzyme120111AI380204breastmetastatic1q32.1Hs.118064similar to rat nuclear ubiquitous casein kinase 2121109U30872breastmetastatic1q32.3Hs.77204centromere protein F 350/400 ka (mitosin)122169U14518breastmetastatic2p23.3Hs.1594centromere protein A 17 kDa123168AI492879breastmetastatic2p25.1Hs.75319ribonucleotide reductase M2 polypeptide124170AL045632breastmetastatic2q33.1Hs.44269hypothetical protein FLJ25211125171N21131breastmetastatic2q37.3Hs.42949hairy and enhancer of split 6 (Drosophila)126191M86699breastmetastatic3p21.31Hs.169840TTK protein kinase127197AA663786breastmetastatic3p21.31NULLunknown128194AI962335breastmetastatic3p24.3Hs.196042ESTs129195AB020713breastmetastatic3p25.1Hs.56966KIAA0906 protein130188AI557210breastmetastatic3q12.3Hs.41271Homo sapiens mRNA full length insert cDNAclone EUROIMAGE 1913076131189X57527breastmetastatic3q12.3Hs.114599collagen type VIII alpha 1132192W02608breastmetastatic3q26.1Hs.36830ESTs Moderately similar to zinc finger protein91 (HPF7 HTF10) [Homo sapiens] [H. sapiens]133193AI760298breastmetastatic3q26.31Hs.128773ESTs134190AI823992breastmetastatic3q26.32Hs.122579epithelial cell transforming sequence 2oncogene135196AI087975breastmetastatic3q28Hs.195225ESTs136201AW001872breastmetastatic5p13.1Hs.58435FYN binding protein (FYB-120/130)137199N90191breastmetastatic5q13.2Hs.23960cyclin B1138200U70370breastmetastatic5q31.1Hs.84136paired-like homeodomain transcription factor 1139198AI739117breastmetastatic5q31.2Hs.73625RAB6 interacting kinesin-like (rabkinesin6)140202D14678breastmetastatic6p21.32Hs.20830kinesin-like 2141204M13436breastmetastatic7p14.1Hs.727inhibin beta A (activin A activin AB alphapolypeptide)142205AA059458breastmetastatic7p14.1Hs.28792Homo sapiens cDNA FLJ11041 fis clonePLACE1004405143203AK023208breastmetastatic7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)144211AI742239breastmetastatic7p15.1Hs.91109Homo sapiens Similar to RIKEN cDNAE130201N16 gene clone IMAGE: 3845782mRNA145208AI285531breastmetastatic7p15.2Hs.106260sorting nexin 10146206AI922323breastmetastatic7p21.1Hs.91011anterior gradient 2 homolog (Xenepus laevis)147209AI961907breastmetastatic7q21.3Hs.179573collagen type I alpha 2148210L37127breastmetastatic7q22.1Hs.80475polymerase (RNA) II (DNA directed)polypeptide J 13.3 kDa149207U61145breastmetastatic7q36.1Hs.77256enhancer of zeste homolog 2 (Drosophila)150220AA625199breastmetastatic8NULLHs.352415solute carrier family 39 (zinc transporter)member 4151223AI949095breastmetastatic8NULLHs.67776Homo sapiens clone IMAGE: 5455669 mRNApartial cds152224W22510breastmetastatic8NULLHs.346950cellular retinoic acid binding protein 1153225AA292431breastmetastatic8NULLHs.92679kinesin family member C2-like154226AI917311breastmetastatic8NULLHs.149152rhophilin 1155212AI932328breastmetastatic8p21.1Hs.104741T-LAK cell-originated protein kinase156213AA203476breastmetastatic8q13.2Hs.252587pituitary tumor-transforming 1157215BE500977breastmetastatic8q13.3Hs.70823sulfatase FP158217BE974098breastmetastatic8q21.13Hs.2384tumor protein D52159219AF091433breastmetastatic8q22.1Hs.30464cyclin E2160222AA610522breastmetastatic8q24.11Hs.162697ESTs161216AA046853breastmetastatic8q24.12Hs.76550mal T-cell differentiation protein 2162218AI656807breastmetastatic8q24.13Hs.222088hypothetical protein MGC5254163221D78130breastmetastatic8q24.13Hs.71465squalene epoxidase164214AA147884breastmetastatic8q24.22Hs.9812Homo sapiens cDNA FLJ14388 fis cloneHEMBA1002716165229AW007586breastmetastatic9q34.11Hs.133122zinc finger DHHC domain containing 12166227W25552breastmetastatic9q34.3Hs.212613hypothetical protein FLJ36779167228AI811865breastmetastatic9q34.3Hs.274152EST168124AF067656breastmetastatic10q21.1Hs.42650ZW10 interactor169123D88357breastmetastatic10q21.2Hs.334562cell division cycle 2 G1 to S and G2 to M170122AI674163breastmetastatic10q23.33Hs.14559hypothetical protein FLJ10540171125U37426breastmetastatic10q23.33Hs.8878kinesin-like 1172131AA705015breastmetastatic11p15.1Hs.185918Homo sapiens cDNA FLJ32525 fis cloneSMINT2000060173129AB018293breastmetastatic11p15.3Hs.314434KIAA0750 gene product174126AL079372breastmetastatic11q13.1Hs.23044similar to RIKEN cDNA 2610036L13175130AF151810breastmetastatic11q13.4Hs.84700serologically defined colon cancer antigen 28176127X14850breastmetastatic11q23.3Hs.147097H2A histone family member X177128AA704137breastmetastatic11q23.3Hs.125359Thy-1 cell surface antigen178132U74612breastmetastatic12p13.33Hs.239forkhead box M1179133U82984breastmetastatic12q13.12Hs.23900Rac GTPase activating protein 1180134R61322breastmetastatic12q24.31Hs.204166Human clone 295 5cM region surroundinghepatocyte nuclear factor-1a/MODY3 mRNA181135AI291142breastmetastatic13q33.3Hs.183874cullin 4A182136L25876breastmetastatic14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)183137AL080146breastmetastatic15q21.3Hs.194698cyclin B2184138D14657breastmetastatic15q22.2Hs.81892KIAA0101 gene product185139AA195614breastmetastatic15q25.3Hs.344037protein regulator of cytokinesis 1186141AW003626breastmetastatic16NULLHs.159154tubulin beta 4187142BC003186breastmetastatic16NULLHs.108196HSPC037 protein188149AI766311breastmetastatic16p12.3Hs.289047Homo sapiens cDNA FLJ14059 fis cloneHEMBB1000573189151AI344053breastmetastatic16p12.3Hs.115838ESTs Highly similar to hypothetical proteinFLJ13593 [Homo sapiens] [H. sapiens]190140AI819340breastmetastatic16p13.3Hs.13561hypothetical protein MGC4692191144W92110breastmetastatic16p13.3Hs.279623selenoprotein × 1192145AI953838breastmetastatic16p13.3Hs.124015hypothetical protein MGC2605193146AL520675breastmetastatic16p13.3Hs.351474hypothetical protein FLJ30002194147BE965311breastmetastatic16p13.3Hs.124915hypothetical protein MGC2601195148AI701742breastmetastatic16p13.3Hs.290943Homo sapiens similar to possible G-proteinreceptor clone MGC: 21993 IMAGE: 4398317mRNA complete cds196150AI655799breastmetastatic16p13.3Hs.197114serine/arginine repetitive matrix 2197143AA904482breastmetastatic16q12.2Hs.368078ESTs198154AI683036breastmetastatic17NULLHs.314169KIAA1618 protein199156U81800breastmetastatic17NULLHs.85838solute carrier family 16 (monocarboxylic acidtransporters) member 3200157BE328850breastmetastatic17q11.2Hs.348504hypothetical protein BC014072201152AW003286breastmetastatic17q21.31Hs.370428ESTs Moderately similar to TP2A_HUMANDNA topoisomerase II alpha isozyme[H. sapiens]202158AI375913breastmetastatic17q21.31Hs.156346topoisomerase (DNA) II alpha 170 kDa203161L47276breastmetastatic17q21.31NULLunknown204162BC001038breastmetastatic17q22Hs.307036Homo sapiens Similar to epsin 3 cloneMGC: 1006 IMAGE: 3505495 mRNA completecds205153AA424160breastmetastatic17q23.2Hs.165909ESTs Weakly similar to hypothetical proteinFLJ20489 [Homo sapiens] [H. sapiens]206164BF029215breastmetastatic17q23.2Hs.103512Homo sapiens cDNA FLJ36569 fis cloneTRACH2010824 highly similar toRibonucleoprotein207155AI675178breastmetastatic17q24.2Hs.90207hypothetical protein MGC11138208163U28386breastmetastatic17q24.3Hs.159557karyopherin alpha 2 (RAG cohort 1 importinalpha 1)209165N42752breastmetastatic17q24.3Hs.42645ESTs210159K02581breastmetastatic17q25.3Hs.105097thymidine kinase 1 soluble211160AI525822breastmetastatic17q25.3Hs.109706hematological and neurological expressed 1212166AF017790breastmetastatic18p11.32Hs.58169highly expressed in cancer rich in leucineheptad repeats213167AA719022breastmetastatic19q13.43Hs.288549ubiquitin UBF-fl214180D80008breastmetastatic20p11.21Hs.36232KIAA0186 gene product215178AI990405breastmetastatic20p11.23Hs.194691retinoic acid induced 3216177AF098158breastmetastatic20q11.1Hs.9329chromosome 20 open reading frame 1217181AW003586breastmetastatic20q11.22Hs.274411SCAN domain containing 1218173U73379breastmetastatic20q13.12Hs.93002ubiquitin-conjugating enzyme E2C219176AI990026breastmetastatic20q13.12Hs.286ribosomal protein L4220182AA207074breastmetastatic20q13.13Hs.56237breast carcinoma amplified sequence 4221174AF041260breastmetastatic20q13.2Hs.129057breast carcinoma amplified sequence 1222183AI638036breastmetastatic20q13.2Hs.189095sal-like 4 (Drosophila)223175AF011468breastmetastatic20q13.31Hs.250822serine/threonine kinase 6224172AA535819breastmetastatic20q13.32Hs.83883transmembrane prostate androgen inducedRNA225179X70940breastmetastatic20q13.33Hs.2642eukaryotic translation elongation factor 1 alpha 2226184AI872267breastmetastatic20q13.33Hs.224895ESTs227186Y15915breastmetastatic22q13.1Hs.172928collagen type I alpha 1228187AL035081breastmetastatic22q13.1Hs.250696KDEL (Lys-Asp-Glu-Leu) endoplasmicreticulum protein retention receptor 3229185AI961206breastmetastatic22q13.2Hs.208912hypothetical protein MGC861230241AK000490colonprimary1p31.2Hs.133260hypothetical protein FLJ20354231235R33352colonprimary1p31.3NULLunknown232233AI739473colonprimary1p32.3Hs.7561624-dehydrocholesterol reductase233239U63743colonprimary1p34.1Hs.69360kinesin-like 6 (mitotic centromere-associatedkinesin)234243U05340colonprimary1p34.2Hs.82906CDC20 cell division cycle 20 homolog (S. cerevisiae)235242AI990026colonprimary1p35.3Hs.286ribosomal protein L4236234T16144colonprimary1q21.3NULLunknown237232AW271106colonprimary1q22Hs.133294ESTs238230AB037776colonprimary1q23.1Hs.38002immunoglobulin superfamily member 9239236AA830844colonprimary1q23.2Hs.127310kinase interacting with leukemia-associatedgene (stathmin)240231AA383718colonprimary1q23.3Hs.234545cell division cycle associated 1241237AI380204colonprimary1q32.1Hs.118064similar to rat nuclear ubiquitous casein kinase 2242240AI990409colonprimary1q32.1Hs.5199HSPC150 protein similar to ubiquitin-conjugating enzyme243238U30872colonprimary1q32.3Hs.77204centromere protein F 350/400 ka (mitosin)244284U14518colonprimary2p23.3Hs.1594centromere protein A 17 kDa245285BE966236colonprimary2p25.1Hs.75319ribonucleotide reductase M2 polypeptide246283AL045632colonprimary2q33.1Hs.44269hypothetical protein FLJ25211247302M86699colonprimary3p21.31Hs.169840TTK protein kinase248301AI962335colonprimary3p24.3Hs.196042ESTs249300AB020713colonprimary3p25.1Hs.56966KIAA0906 protein250304X57527colonprimary3q12.3Hs.114599collagen type VIII alpha 1251305AI557210colonprimary3q12.3Hs.41271Homo sapiens mRNA full length insert cDNAclone EUROIMAGE 1913076252303AI823992colonprimary3q26.32Hs.122579epithelial cell transforming sequence 2oncogene253299AI087975colonprimary3q28Hs.195225ESTs254307AW001872colonprimary5p13.1Hs.58435FYN binding protein (FYB-120/130)255306M25753colonprimary5q13.2Hs.23960cyclin B1256308U70370colonprimary5q31.1Hs.84136paired-like homeodomain transcription factor 1257309AI739117colonprimary5q31.2Hs.73625RAB6 interacting kinesin-like (rabkinesin6)258310D14678colonprimary6p21.32Hs.20830kinesin-like 2259313AA059458colonprimary7p14.1Hs.28792Homo sapiens cDNA FLJ11041 fis clonePLACE1004405260315M13436colonprimary7p14.1Hs.727inhibin beta A (activin A activin AB alphapolypeptide)261314AI341261colonprimary7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)262312AI922323colonprimary7p21.1Hs.91011anterior gradient 2 homolog (Xenepus laevis)263311U61145colonprimary7q36.1Hs.77256enhancer of zeste homolog 2 (Drosophila)264316AI949095colonprimary8NULLHs.67776Homo sapiens clone IMAGE: 5455669 mRNApartial cds265318AA625199colonprimary8NULLHs.352415solute carrier family 39 (zinc transporter)member 4266325AI932328colonprimary8p21.1Hs.104741T-LAK cell-originated protein kinase267324AA203476colonprimary8q13.2Hs.252587pituitary tumor-transforming 1268323AW043713colonprimary8q13.3Hs.70823sulfatase FP269319AF091433colonprimary8q22.1Hs.30464cyclin E2270321AL117612colonprimary8q24.12Hs.76550mal T-cell differentiation protein 2271317D78130colonprimary8q24.13Hs.71465squalene epoxidase272320AI656807colonprimary8q24.13Hs.222088hypothetical protein MGC5254273322AA147884colonprimary8q24.22Hs.9812Homo sapiens cDNA FLJ14388 fis cloneHEMBA1002716274326AW007586colonprimary9q34.11Hs.133122zinc finger DHHC domain containing 12275327AI811865colonprimary9q34.3Hs.274152EST276328W25552colonprimary9q34.3Hs.212613hypothetical protein FLJ36779277244AF067656colonprimary10q21.1Hs.42650ZW10 interactor278245AL524035colonprimary10q21.2Hs.334562cell division cycle 2 G1 to S and G2 to M279246AI674163colonprimary10q23.33Hs.14559hypothetical protein FLJ10540280248AB018293colonprimary11p15.3Hs.314434KIAA0750 gene product281251AL079372colonprimary11q13.1Hs.23044similar to RIKEN cDNA 2610036L13282247D60944colonprimary11q13.4Hs.84700serologically defined colon cancer antigen 28283249AA704137colonprimary11q23.3Hs.125359Thy-1 cell surface antigen284250X14850colonprimary11q23.3Hs.147097H2A histone family member X285253U74612colonprimary12p13.33Hs.239forkhead box M1286252U82984colonprimary12q13.12Hs.23900Rac GTPase activating protein 1287254AI291142colonprimary13q33.3Hs.183874cullin 4A288255L25876colonprimary14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)289258AL080146colonprimary15q21.3Hs.194698cyclin B2290257D14657colonprimary15q22.2Hs.81892KIAA0101 gene product291256AA195614colonprimary15q25.3Hs.344037protein regulator of cytokinesis 1292265BC003186colonprimary16NULLHs.108196HSPC037 protein293266AW003626colonprimary16NULLHs.159154tubulin beta 4294259AI701742colonprimary16p13.3Hs.290943Homo sapiens similar to possible G-proteinreceptor clone MGC: 21993 IMAGE: 4398317mRNA complete cds295260BE965311colonprimary16p13.3Hs.124915hypothetical protein MGC2601296261AL520675colonprimary16p13.3Hs.351474hypothetical protein FLJ30002297262AI953838colonprimary16p13.3Hs.124015hypothetical protein MGC2605298263W92110colonprimary16p13.3Hs.279623selenoprotein × 1299267AI819340colonprimary16p13.3Hs.13561hypothetical protein MGC4692300264AA904482colonprimary16q12.2Hs.368078ESTs301276U81800colonprimary17NULLHs.85838solute carrier family 16 (monocarboxylic acidtransporters) member 3302278AI683036colonprimary17NULLHs.314169KIAA1618 protein303275BE328850colonprimary17q11.2Hs.348504hypothetical protein BC014072304272L47276colonprimary17q21.31NULLunknown305274AI375913colonprimary17q21.31Hs.156346topoisomerase (DNA) II alpha 170 kDa306280AW003286colonprimary17q21.31Hs.370428ESTs Moderately similar to TP2A_HUMANDNA topoisomerase II alpha isozyme[H. sapiens]307271BC001038colonprimary17q22Hs.307036Homo sapiens Similar to epsin 3 cloneMGC: 1006 IMAGE: 3505495 mRNA completecds308269BF029215colonprimary17q23.2Hs.103512Homo sapiens cDNA FLJ36569 fis cloneTRACH2010824 highly similar toRibonucleoprotein309279BG165011colonprimary17q23.2Hs.165909ESTs Weakly similar to hypothetical proteinFLJ20489 [Homo sapiens] [H. sapiens]310277AI675178colonprimary17q24.2Hs.90207hypothetical protein MGC11138311270U28386colonprimary17q24.3Hs.159557karyopherin alpha 2 (RAG cohort 1 importinalpha 1)312268AI525822colonprimary17q25.3Hs.109706hematological and neurological expressed 1313273K02581colonprimary17q25.3Hs.105097thymidine kinase 1 soluble314281AF017790colonprimary18p11.32Hs.58169highly expressed in cancer rich in leucineheptad repeats315282AA719022colonprimary19q13.43Hs.288549ubiquitin UBF-fl316288D80008colonprimary20p11.21Hs.36232KIAA0186 gene product317290AI990405colonprimary20p11.23Hs.194691retinoic acid induced 3318291AF098158colonprimary20q11.1Hs.9329chromosome 20 open reading frame 1319287AW003586colonprimary20q11.22Hs.274411SCAN domain containing 1320294U73379colonprimary20q13.12Hs.93002ubiquitin-conjugating enzyme E2C321286AA207074colonprimary20q13.13Hs.56237breast carcinoma amplified sequence 4322293AF041260colonprimary20q13.2Hs.129057breast carcinoma amplified sequence 1323292AF011468colonprimary20q13.31Hs.250822serine/threonine kinase 6324295AA535819colonprimary20q13.32Hs.83883transmembrane prostate androgen inducedRNA325289X70940colonprimary20q13.33Hs.2642eukaryotic translation elongation factor 1 alpha 2326296AL035081colonprimary22q13.1Hs.250696KDEL (Lys-Asp-Glu-Leu) endoplasmicreticulum protein retention receptor 3327297Y15916colonprimary22q13.1Hs.172928collagen type I alpha 1328298AI381686colonprimary22q13.2Hs.208912hypothetical protein MGC861329420AK000490colonmetastatic1p31.2Hs.133260hypothetical protein FLJ20354330354R33352colonmetastatic1p31.3NULLunknown331351AI739473colonmetastatic1p32.3Hs.7561624-dehydrocholesterol reductase332396U63743colonmetastatic1p34.1Hs.69360kinesin-like 6 (mitotic centromere-associatedkinesin)333425U05340colonmetastatic1p34.2Hs.82906CDC20 cell division cycle 20 homolog (S. cerevisiae)334421AI990026colonmetastatic1p35.3Hs.286ribosomal protein L4335352T16144colonmetastatic1q21.3NULLunknown336346AW271106colonmetastatic1q22Hs.133294ESTs337340AB037776colonmetastatic1q23.1Hs.38002immunoglobulin superfamily member 9338357AA830844colonmetastatic1q23.2Hs.127310kinase interacting with leukemia-associatedgene (stathmin)339330AF326731colonmetastatic1q23.3Hs.234545cell division cycle associated 1340341AI983896colonmetastatic1q23.3Hs.191187ESTs341380AF326731colonmetastatic1q23.3Hs.234545cell division cycle associated 1342360AI380204colonmetastatic1q32.1Hs.118064similar to rat nuclear ubiquitous casein kinase 2343403AI990409colonmetastatic1q32.1Hs.5199HSPC150 protein similar to ubiquitin-conjugating enzyme344382U30872colonmetastatic1q32.3Hs.77204centromere protein F 350/400 ka (mitosin)345400U14518colonmetastatic2p23.3Hs.1594centromere protein A 17 kDa346419BE966236colonmetastatic2p25.1Hs.75319ribonucleotide reductase M2 polypeptide347349AL045632colonmetastatic2q33.1Hs.44269hypothetical protein FLJ25211348365M86699colonmetastatic3p21.31Hs.169840TTK protein kinase349334AI962335colonmetastatic3p24.3Hs.196042ESTs350333AB020713colonmetastatic3p25.1Hs.56966KIAA0906 protein351412X57527colonmetastatic3q12.3Hs.114599collagen type VIII alpha 1352417AI557210colonmetastatic3q12.3Hs.41271Homo sapiens mRNA full length insert cDNAclone EUROIMAGE 1913076353344W02608colonmetastatic3q26.1Hs.36830ESTs Moderately similar to zinc finger protein91 (HPF7 HTF10) [Homo sapiens] [H. sapiens]354395AI823992colonmetastatic3q26.32Hs.122579epithelial cell transforming sequence 2oncogene355332AI087975colonmetastatic3q28Hs.195225ESTs356409AW001872colonmetastatic5p13.1Hs.58435FYN binding protein (FYB-120/130)357408M25753colonmetastatic5q13.2Hs.23960cyclin B1358410U70370colonmetastatic5q31.1Hs.84136paired-like homeodomain transcription factor 1359434AI739117colonmetastatic5q31.2Hs.73625RAB6 interacting kinesin-like (rabkinesin6)360389D14678colonmetastatic6p21.32Hs.20830kinesin-like 2361427AA059458colonmetastatic7p14.1Hs.28792Homo sapiens cDNA FLJ11041 fis clonePLACE1004405362436AI343467colonmetastatic7p14.1Hs.28792Homo sapiens cDNA FLJ11041 fis clonePLACE1004405363437M13436colonmetastatic7p14.1Hs.727inhibin beta A (activin A activin AB alphapolypeptide)364329AK023208colonmetastatic7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)365438AK023208colonmetastatic7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)366440AK023208colonmetastatic7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)367348AI285531colonmetastatic7p15.2Hs.106260sorting nexin 10368392AI922323colonmetastatic7p21.1Hs.91011anterior gradient 2 homolog (Xenepus laevis)369339AI961907colonmetastatic7q21.3Hs.179573collagen type I alpha 2370356U61145colonmetastatic7q36.1Hs.77256enhancer of zeste homolog 2 (Drosophila)371336AI949095colonmetastatic8NULLHs.67776Homo sapiens clone IMAGE: 5455669 mRNApartial cds372362AA625199colonmetastatic8NULLHs.352415solute carrier family 39 (zinc transporter)member 4373439AI932328colonmetastatic8p21.1Hs.104741T-LAK cell-originated protein kinase374428AA203476colonmetastatic8q13.2Hs.252587pituitary tumor-transforming 1375414AW043713colonmetastatic8q13.3Hs.70823sulfatase FP376345AA524023colonmetastatic8q21.13Hs.2384tumor protein D52377363AF091433colonmetastatic8q22.1Hs.30464cyclin E2378342AA610522colonmetastatic8q24.11Hs.162697ESTs379373AL117612colonmetastatic8q24.12Hs.76550mal T-cell differentiation protein 2380347D78130colonmetastatic8q24.13Hs.71465squalene epoxidase381366AI656807colonmetastatic8q24.13Hs.222088hypothetical protein MGC5254382388AA147884colonmetastatic8q24.22Hs.9812Homo sapiens cDNA FLJ14388 fis cloneHEMBA1002716383374AW007586colonmetastatic9q34.11Hs.133122zinc finger DHHC domain containing 12384383AI811865colonmetastatic9q34.3Hs.274152EST385393W25552colonmetastatic9q34.3Hs.212613hypothetical protein FLJ36779386355AF067656colonmetastatic10q21.1Hs.42650ZW10 interactor387368X05360colonmetastatic10q21.2Hs.334562cell division cycle 2 G1 to S and G2 to M388416AI674163colonmetastatic10q23.33Hs.14559hypothetical protein FLJ10540389337AA705015colonmetastatic11p15.1Hs.185918Homo sapiens cDNA FLJ32525 fis cloneSMINT2000060390372AB018293colonmetastatic11p15.3Hs.314434KIAA0750 gene product391401AL079372colonmetastatic11q13.1Hs.23044similar to RIKEN cDNA 2610036L13392350D60944colonmetastatic11q13.4Hs.84700serologically defined colon cancer antigen 28393379AA704137colonmetastatic11q23.3Hs.125359Thy-1 cell surface antigen394381X14850colonmetastatic11q23.3Hs.147097H2A histone family member X395429U74612colonmetastatic12p13.33Hs.239forkhead box M1396384U82984colonmetastatic12q13.12Hs.23900Rac GTPase activating protein 1397343R61322colonmetastatic12q24.31Hs.204166Human clone 295 5cM region surroundinghepatocyte nuclear factor-1a/MODY3 mRNA398353AI291142colonmetastatic13q33.3Hs.183874cullin 4A399387L25876colonmetastatic14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)400423AL080146colonmetastatic15q21.3Hs.194698cyclin B2401413D14657colonmetastatic15q22.2Hs.81892KIAA0101 gene product402406AA195614colonmetastatic15q25.3Hs.344037protein regulator of cytokinesis 1403407BC003186colonmetastatic16NULLHs.108196HSPC037 protein404415AW003626colonmetastatic16NULLHs.159154tubulin beta 4405358AI701742colonmetastatic16p13.3Hs.290943Homo sapiens similar to possible G-proteinreceptor clone MGC: 21993 IMAGE: 4398317mRNA complete cds406361BE965311colonmetastatic16p13.3Hs.124915hypothetical protein MGC2601407364AL520675colonmetastatic16p13.3Hs.351474hypothetical protein FLJ30002408377AI953838colonmetastatic16p13.3Hs.124015hypothetical protein MGC2605409385W92110colonmetastatic16p13.3Hs.279623selenoprotein × 1410431AI819340colonmetastatic16p13.3Hs.13561hypothetical protein MGC4692411405AA904482colonmetastatic16q12.2Hs.368078ESTs412391U81800colonmetastatic17NULLHs.85838solute carrier family 16 (monocarboxylic acidtransporters) member 3413411AI683036colonmetastatic17NULLHs.314169KIAA1618 protein414390BE328850colonmetastatic17q11.2Hs.348504hypothetical protein BC014072415376L47276colonmetastatic17q21.31NULLunknown416386AI375913colonmetastatic17q21.31Hs.156346topoisomerase (DNA) II alpha 170 kDa417432AW003286colonmetastatic17q21.31Hs.370428ESTs Moderately similar to TP2A_HUMANDNA topoisomerase II alpha isozyme[H. sapiens]418375BC001038colonmetastatic17q22Hs.307036Homo sapiens Similar to epsin 3 cloneMGC: 1006 IMAGE: 3505495 mRNA completecds419359BF029215colonmetastatic17q23.2Hs.103512Homo sapiens cDNA FLJ36569 fis cloneTRACH2010824 highly similar toRibonucleoprotein420426BG165011colonmetastatic17q23.2Hs.165909ESTs Weakly similar to hypothetical proteinFLJ20489 [Homo sapiens] [H. sapiens]421398AI675178colonmetastatic17q24.2Hs.90207hypothetical protein MGC11138422369U28386colonmetastatic17q24.3Hs.159557karyopherin alpha 2 (RAG cohort 1 importinalpha 1)423335AI525822colonmetastatic17q25.3Hs.109706hematological and neurological expressed 1424378K02581colonmetastatic17q25.3Hs.105097thymidine kinase 1 soluble425331AF017790colonmetastatic18p11.32Hs.58169highly expressed in cancer rich in leucineheptad repeats426404AF017790colonmetastatic18p11.32Hs.58169highly expressed in cancer rich in leucineheptad repeats427422AA719022colonmetastatic19q13.43Hs.288549ubiquitin UBF-fl428371D80008colonmetastatic20p11.21Hs.36232KIAA0186 gene product429399AI990405colonmetastatic20p11.23Hs.194691retinoic acid induced 3430402AF098158colonmetastatic20q11.1Hs.9329chromosome 20 open reading frame 1431370AW003586colonmetastatic20q11.22Hs.274411SCAN domain containing 1432433U73379colonmetastatic20q13.12Hs.93002ubiquitin-conjugating enzyme E2C433338AA207074colonmetastatic20q13.13Hs.56237breast carcinoma amplified sequence 4434430AF041260colonmetastatic20q13.2Hs.129057breast carcinoma amplified sequence 1435424AF011468colonmetastatic20q13.31Hs.250822serine/threonine kinase 6436435AA535819colonmetastatic20q13.32Hs.83883transmembrane prostate androgen inducedRNA437394X70940colonmetastatic20q13.33Hs.2642eukaryotic translation elongation factor 1 alpha 2438367AL035081colonmetastatic22q13.1Hs.250696KDEL (Lys-Asp-Glu-Leu) endoplasmicreticulum protein retention receptor 3439397Y15916colonmetastatic22q13.1Hs.172928collagen type I alpha 1440418AI381686colonmetastatic22q13.2Hs.208912hypothetical protein MGC861441506AA905821lungprimary1p31.3Hs.145958ESTs442508AI056599lungprimary1p31.3Hs.120893ESTs443511AW070459lungprimary1p31.3Hs.259438ESTs444527AK022113lungprimary1p31.3Hs.301858Homo sapiens cDNA FLJ13017 fis cloneNT2RP3000628445528AU151151lungprimary1p31.3Hs.11493Homo sapiens cDNA FLJ13536 fis clonePLACE1006521446547AB044807lungprimary1p31.3Hs.321197PDZ domain protein (Drosophila inaD-like)447485AA012917lungprimary1p32.1Hs.333541beta-amyloid binding protein precursor448498BF224444lungprimary1p32.1Hs.127274ESTs449526AU147177lungprimary1p32.1Hs.301237Homo sapiens cDNA FLJ12095 fis cloneHEMBB1002610450473AA926959lungprimary1q21.3Hs.77550p53-regulated DDA3451443AI053741lungprimary1q22Hs.133294ESTs452448AI766666lungprimary1q22Hs.374850apolipoprotein A-I binding protein453469AI739071lungprimary1q22Hs.158515hypothetical protein MGC13038454441AF326731lungprimary1q23.3Hs.234545cell division cycle associated 1455446BC002906lungprimary1q23.3Hs.75939uridine monophosphate kinase456442AA182412lungprimary1q25.3Hs.32058chromosome 1 open reading frame 19457482AA725362lungprimary2p11.1NULLunknown458472AI990317lungprimary2p13.1Hs.154672methylene tetrahydrofolate dehydrogenase(NAD+ dependent) methenyltetrahydrofolatecyclohydrolase459464AI191897lungprimary2p16.2Hs.105223Homo sapiens Similar to RIKEN cDNA2510006C20 gene clone MGC: 24001IMAGE: 4050858 mRNA complete cds460474AI492879lungprimary2p25.1Hs.75319ribonucleotide reductase M2 polypeptide461481H24953lungprimary2q13NULLunknown462451AA749314lungprimary2q31.1Hs.333893cell division cycle associated 7463519C00851lungprimary5p13.2Hs.144264ESTs Weakly similar to hypothetical proteinFLJ20837 [Homo sapiens] [H. sapiens]464458AA383208lungprimary5p15.1Hs.125249ESTs465548AA524353lungprimary6p21.2Hs.27693peptidylprolyl isomerase (cyclophilin)-like 1466522AW005489lungprimary6p21.31Hs.139800high mobility group AT-hook 1467538AI677701lungprimary6p22.3Hs.201619hypothetical protein FLJ30829468551BG528420lungprimary6p22.3Hs.83484SRY (sex determining region Y)-box 4469467AI439141lungprimary6p23Hs.261023hypothetical protein FLJ20958470539AI279547lungprimary6p24.1Hs.8645hypothetical protein LOC51256471540W27692lungprimary6p24.2Hs.273077hypothetical protein MGC1223472495K03193lungprimary7p11.2Hs.77432epidermal growth factor receptor(erythroblastic leukemia viral (v-erb-b)oncogene homolog avian)473496AI806160lungprimary7p11.2Hs.127991ESTs474497AW138673lungprimary7p11.2Hs.252928ESTs475502H65306lungprimary7p11.2Hs.205559ESTs476509AW971863lungprimary7p11.2Hs.103351ESTs477536D60436lungprimary7p11.2Hs.335933Homo sapiens clone MGC: 33530IMAGE: 4820705 mRNA complete cds478545AI363001lungprimary7p11.2Hs.134342LanC lantibiotic synthetase component C-like2 (bacterial)479524AV700815lungprimary7p12.3Hs.180171Homo sapiens cDNA FLJ10417 fis cloneNT2RP1000112480486AA740186lungprimary7p13Hs.81029biliverdin reductase A481510AI252004lungprimary7p13Hs.284148ESTs482514AW452419lungprimary7p13Hs.296098ESTs483515AI418313lungprimary7p13Hs.152895ESTs484517AI191118lungprimary7p13Hs.222015ESTs Moderately similar to cytokine receptor-like factor 2 cytokine receptor CRL2 precusor[Homo sapiens]485523AI823792lungprimary7p13Hs.301005histone H2A.F/Z variant486533AK025276lungprimary7p13Hs.306791Homo sapiens cDNA: FLJ21623 fis cloneCOL07915487534AL137266lungprimary7p13Hs.332520Homo sapiens mRNA cDNA DKFZp434A1014(from clone DKFZp434A1014) partial cds488542BC004903lungprimary7p13Hs.9960hypothetical protein MGC4607489546AF192523lungprimary7p13Hs.47701NPC1 (Niemann-Pick disease type C1 gene)-like 1490550AW194730lungprimary7p13Hs.9075serine/threonine kinase 17a (apoptosis-inducing)491541BC000769lungprimary7p14.1Hs.59594hypothetical protein MGC2821492445U97188lungprimary7p15.3Hs.79440IGF-II mRNA-binding protein 3493465AI910524lungprimary7p15.3Hs.87385hypothetical protein BC012331494471AI806483lungprimary7p15.3Hs.108931membrane protein palmitoylated 6 (MAGUKp55 subfamily member 6)495494AW402635lungprimary7q22.1Hs.375569DNA directed RNA polymerase II polypeptideJ-related gene496475AI922792lungprimary8NULLHs.239784scribble497489R51273lungprimary8q12.2Hs.250502carbonic anhydrase VIII498500BE465243lungprimary8q13.2Hs.12664ESTs499503AA132172lungprimary8q13.2Hs.19107ESTs500549AA203476lungprimary8q13.2Hs.252587pituitary tumor-transforming 1501555AF232217lungprimary8q13.3NULLunknown502556AF130055lungprimary8q13.3NULLunknown503463BF002104lungprimary8q21.11Hs.168950Homo sapiens mRNA cDNA DKFZp566A1046(from clone DKFZp566A1046)504507AI335223lungprimary8q21.11Hs.133293ESTs505512AI370381lungprimary8q21.11Hs.128841ESTs506529AK024242lungprimary8q21.11Hs.296753Homo sapiens cDNA FLJ14180 fis cloneNT2RP2003799507530AI701468lungprimary8q21.11Hs.60681Homo sapiens cDNA FLJ34367 fis cloneFEBRA2016621508480BG389015lungprimary8q21.13Hs.2384tumor protein D52509499AA479492lungprimary8q21.13Hs.184387ESTs510488U07969lungprimary8q22.1Hs.89436cadherin 17 LI cadherin (liver-intestine)511491AF091433lungprimary8q22.1Hs.30464cyclin E2512490AA584310lungprimary8q22.3Hs.283713collagen triple helix repeat containing 1513505AA904882lungprimary8q22.3Hs.130107ESTs514543AA451665lungprimary8q24.13Hs.222088hypothetical protein MGC5254515493W03103lungprimary8q24.22Hs.10669development and differentiation enhancingfactor 1516518BF055351lungprimary8q24.22Hs.20247ESTs Weakly similar to hypothetical proteinFLJ20489 [Homo sapiens] [H. sapiens]517544BF941325lungprimary8q24.22Hs.15611KIAA1485 protein518535AW137073lungprimary8q24.23Hs.176669Homo sapiens mRNA cDNA DKFZp451M139(from clone DKFZp451M139)519537AA447947lungprimary12p11.22Hs.227591hypothetical protein FLJ11088520456R91766lungprimary12p11.23Hs.173074DKFZP564O1863 protein521466AF274950lungprimary12p11.23Hs.22595hypothetical protein FLJ10637522470AI334297lungprimary12p11.23Hs.51743KIAA1340 protein523476AW779556lungprimary12p11.23Hs.184523serine/threonine kinase 38 like524478AI688580lungprimary12p11.23Hs.286145SRB7 suppressor of RNA polymerase Bhomolog (yeast)525483AF161472lungprimary12p11.23NULLunknown526504BF724206lungprimary12p11.23Hs.221024ESTs527525AL118653lungprimary12p11.23Hs.284270Homo sapiens cDNA FLJ11335 fis clonePLACE1010630528531AI652982lungprimary12p11.23Hs.111583Homo sapiens cDNA FLJ34764 fis cloneNT2NE2002311529553AA127950lungprimary12p11.23Hs.222024transcription factor BMAL2530449AI652662lungprimary12p12.1Hs.317432branched chain aminotransferase 1 cytosolic531460AU154905lungprimary12p12.1Hs.296734Homo sapiens cDNA FLJ13318 fis cloneOVARC1001600532461AK025615lungprimary12p12.1Hs.7567Homo sapiens cDNA: FLJ21962 fis cloneHEP05564533462AA829940lungprimary12p12.1Hs.301210Homo sapiens mRNA cDNA DKFZp564F2072(from clone DKFZp564F2072)534468BE326710lungprimary12p12.1Hs.170994hypothetical protein MGC10946535484AA015609lungprimary12p12.1Hs.351221v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogenehomolog536501W70242lungprimary12p12.1Hs.58086ESTs537516AI242023lungprimary12p12.1Hs.137003ESTs538520AI003792lungprimary12p12.1Hs.120439ethanolamine kinase539554AA669106lungprimary12p12.2Hs.108106ubiquitin-like containing PHD and RING fingerdomains 1540459BC003602lungprimary12p12.3Hs.36727H2A histone family member J541487AI392836lungprimary12p13.31Hs.12045C2f protein542492AI983033lungprimary12p13.31Hs.380623DEAD/H (Asp-Glu-Ala-Asp/His) boxpolypeptide 11 (CHL1-like helicase homolog S. cerevisiae)543521U74612lungprimary12p13.33Hs.239forkhead box M1544455AF213033lungprimary14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)545447AF167438lungprimary14q23.2Hs.179817androgen-regulated short-chaindehydrogenase/reductase 1546513AI146765lungprimary18p11.31Hs.373550ESTs547532AW003207lungprimary18p11.31Hs.48659Homo sapiens cDNA FLJ36057 fis cloneTESTI2018475 highly similar to LAMININALPHA-1 CHAIN PRECURSOR548444AF017790lungprimary18p11.32Hs.58169highly expressed in cancer rich in leucineheptad repeats549450AB023169lungprimary20p12.2Hs.7935BTB (POZ) domain containing 3550457AI732446lungprimary20p12.2Hs.70903ESTs551479D21267lungprimary20p12.2Hs.84389synaptosomal-associated protein 25 kDa552452Y00064lungprimary20p12.3Hs.2281chromogranin B (secretogranin 1)553453AI096882lungprimary20p13Hs.135056chromosome 20 open reading frame 139554454AI949781lungprimary20p13Hs.26802chromosome 20 open reading frame 97555477AI924533lungprimary20p13Hs.105607solute carrier family 4 sodium bicarbonatetransporter-like member 11556552U85658lungprimary20q13.31Hs.61796transcription factor AP-2 gamma (activatingenhancer binding protein 2 gamma)557654AW151887lungmetastatic1p22.3Hs.169939heparan sulfate 2-O-sulfotransferase 1558651BE645144lungmetastatic1p31.1Hs.374411ESTs Moderately similar to hypotheticalprotein FLJ20378 [Homo sapiens] [H. sapiens]559619AI810054lungmetastatic1p31.2Hs.133260hypothetical protein FLJ20354560629N32508lungmetastatic1p31.2Hs.8107G-protein gamma-12 subunit561636BC002488lungmetastatic1p31.2Hs.165998PAI-1 mRNA-binding protein562628AA618420lungmetastatic1p32.1Hs.299254Homo sapiens cDNA: FLJ23597 fis cloneLNG15281563627AW140098lungmetastatic1p32.3Hs.25821Fas (TNFRSF6) associated factor 1564648AW409848lungmetastatic1p32.3Hs.13036DKFZP727A071 protein565637AF151063lungmetastatic1p34.1NULLunknown566600AA926959lungmetastatic1q21.3Hs.77550p53-regulated DDA3567576AI766666lungmetastatic1q22Hs.374850apolipoprotein A-I binding protein568588AI690773lungmetastatic1q22Hs.133294ESTs569601AI739071lungmetastatic1q22Hs.158515hypothetical protein MGC13038570561AF326731lungmetastatic1q23.3Hs.234545cell division cycle associated 1571562D78335lungmetastatic1q23.3Hs.75939uridine monophosphate kinase572558AA182412lungmetastatic1q25.3Hs.32058chromosome 1 open reading frame 19573599AA725362lungmetastatic2p11.1NULLunknown574592AI990317lungmetastatic2p13.1Hs.154672methylene tetrahydrofolate dehydrogenase(NAD+ dependent) methenyltetrahydrofolatecyclohydrolase575603AI191897lungmetastatic2p16.2Hs.105223Homo sapiens Similar to RIKEN cDNA2510006C20 gene clone MGC: 24001IMAGE: 4050858 mRNA complete cds576583BC001886lungmetastatic2p25.1Hs.75319ribonucleotide reductase M2 polypeptide577605H24953lungmetastatic2q13NULLunknown578575AA749314lungmetastatic2q31.1Hs.333893cell division cycle associated 7579579AA868748lungmetastatic5p15.1Hs.125249ESTs580589AI439141lungmetastatic6p23Hs.261023hypothetical protein FLJ20958581606AU156822lungmetastatic7p11.2Hs.287577Homo sapiens cDNA FLJ13503 fis clonePLACE1004838582607U48722lungmetastatic7p11.2NULLunknown583609AA768884lungmetastatic7p11.2Hs.140489Homo sapiens cDNA FLJ25559 fis cloneJTH02834584610AK000106lungmetastatic7p11.2Hs.272227Homo sapiens cDNA FLJ20099 fis cloneCOL04544585613AU147861lungmetastatic7p11.2Hs.188082Homo sapiens cDNA FLJ12308 fis cloneMAMMA1001931586616BE737030lungmetastatic7p11.2Hs.82916chaperonin containing TCP1 subunit 6A (zeta1)587622AW157070lungmetastatic7p11.2Hs.77432epidermal growth factor receptor(erythroblastic leukemia viral (v-erb-b)oncogene homolog avian)588639BE878463lungmetastatic7p11.2Hs.279898Homo sapiens cDNA: FLJ23165 fis cloneLNG09846589557AK023208lungmetastatic7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)590560U97188lungmetastatic7p15.3Hs.79440IGF-II mRNA-binding protein 3591577AI910524lungmetastatic7p15.3Hs.87385hypothetical protein BC012331592590AI806483lungmetastatic7p15.3Hs.108931membrane protein palmitoylated 6 (MAGUKp55 subfamily member 6)593617AL136770lungmetastatic7q21.13Hs.258576claudin 12594635BF680588lungmetastatic7q21.13Hs.118258Homo sapiens cDNA: FLJ23160 fis cloneLNG09682595618U19348lungmetastatic7q31.2NULLunknown596638BG170541lungmetastatic7q31.2Hs.285754met proto-oncogene (hepatocyte growth factorreceptor)597641AI632244lungmetastatic7q32.1Hs.233694putative methyltransferase598653AI964022lungmetastatic7q33Hs.107394secretory protein SEC8599593AI922792lungmetastatic8NULLHs.239784scribble600644AA723810lungmetastatic8NULLHs.69517cDNA for differentially expressed CO16 gene601621BF059124lungmetastatic8q12.3Hs.29419ESTs602631AA543030lungmetastatic8q12.3Hs.152409ESTs603632AF289489lungmetastatic8q12.3Hs.283664aspartate beta-hydroxylase604646AW663544lungmetastatic8q13.1Hs.85524ring finger protein 29605581BF002104lungmetastatic8q21.11Hs.168950Homo sapiens mRNA cDNA DKFZp566A1046(from clone DKFZp566A1046)606612AI916600lungmetastatic8q21.11Hs.121194Homo sapiens cDNA: FLJ21569 fis cloneCOL06508607623AI625741lungmetastatic8q21.11Hs.21275hypothetical protein FLJ11011608630AW150720lungmetastatic8q21.11Hs.356086ESTs Weakly similar to retinal short-chaindehydrogenase/reductase retSDR2 [Homosapiens] [H. sapiens]609645N89607lungmetastatic8q21.11Hs.184693transcription elongation factor B (SIII)polypeptide 1 (15 kDa elongin C)610650W46994lungmetastatic8q21.11Hs.96870staufen RNA binding protein homolog 2(Drosophila)611563BG389015lungmetastatic8q21.13Hs.2384tumor protein D52612633AK000049lungmetastatic8q21.13Hs.183861hypothetical protein MGC22825613634AK024296lungmetastatic8q21.13Hs.237146zinc finger protein RINZF614656AL039862lungmetastatic8q24.21Hs.49136Homo sapiens cDNA FLJ23705 fis cloneHEP11066615611M26095lungmetastatic11p15.2Hs.37058calcitonin/calcitonin-related polypeptide alpha616565AF256215lungmetastatic12p11.23Hs.222024transcription factor BMAL2617566AI569851lungmetastatic12p11.23Hs.22595hypothetical protein FLJ10637618573AF161472lungmetastatic12p11.23NULLunknown619574U46837lungmetastatic12p11.23Hs.286145SRB7 suppressor of RNA polymerase Bhomolog (yeast)620580R91766lungmetastatic12p11.23Hs.173074DKFZP564O1863 protein621584AI334297lungmetastatic12p11.23Hs.51743KIAA1340 protein622585AW779556lungmetastatic12p11.23Hs.184523serine/threonine kinase 38 like623586BF540749lungmetastatic12p11.23Hs.111583Homo sapiens cDNA FLJ34764 fis cloneNT2NE2002311624587BC005176lungmetastatic12p11.23Hs.10071seven transmembrane protein TM7SF3625564AI652662lungmetastatic12p12.1Hs.317432branched chain aminotransferase 1 cytosolic626568AK025615lungmetastatic12p12.1Hs.7567Homo sapiens cDNA: FLJ21962 fis cloneHEP05564627570BE326710lungmetastatic12p12.1Hs.170994hypothetical protein MGC10946628595AA829940lungmetastatic12p12.1Hs.301210Homo sapiens mRNA cDNA DKFZp564F2072(from clone DKFZp564F2072)629597AA015609lungmetastatic12p12.1Hs.351221v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogenehomolog630604AU154905lungmetastatic12p12.1Hs.296734Homo sapiens cDNA FLJ13318 fis cloneOVARC1001600631571AK025578lungmetastatic12p12.2Hs.108106ubiquitin-like containing PHD and RING fingerdomains 1632578BC003602lungmetastatic12p12.3Hs.36727H2A histone family member J633643AI743489lungmetastatic12p13.1Hs.322679Homo sapiens cDNA FLJ36082 fis cloneTESTI2019998634642AA102574lungmetastatic14q12Hs.8858bromodomain adjacent to zinc finger domain1A635620AI953589lungmetastatic14q13.1Hs.146134ESTs636608AW268365lungmetastatic14q21.3Hs.25740ERO1-like (S. cerevisiae)637626BC006117lungmetastatic14q21.3Hs.222021hypothetical protein FLJ12618638655AJ292969lungmetastatic14q21.3Hs.288906WW45 protein639567AF213033lungmetastatic14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)640652BC005359lungmetastatic14q22.1Hs.151413glia maturation factor beta641614AI985034lungmetastatic14q23.1Hs.2704glutathione peroxidase 2 (gastrointestinal)642624AI554514lungmetastatic14q23.1Hs.97849ESTs643569AF167438lungmetastatic14q23.2Hs.179817androgen-regulated short-chaindehydrogenase/reductase 1644625AI654093lungmetastatic14q23.2Hs.43397Homo sapiens cDNA FLJ37574 fis cloneBRCOC2003100645647BE465894lungmetastatic14q24.2Hs.98365hypothetical protein FLJ39091646615AI969102lungmetastatic14q32.11Hs.172216chromogranin A (parathyroid secretory protein1)647640AI656232lungmetastatic14q32.11Hs.90034hypothetical protein FLJ21916648649AI670847lungmetastatic14q32.12Hs.374662Homo sapiens cDNA FLJ40513 fis cloneTESTI2046456649559AF017790lungmetastatic18p11.32Hs.58169highly expressed in cancer rich in leucineheptad repeats650591D21267lungmetastatic20p12.2Hs.84389synaptosomal-associated protein 25 kDa651598AI732446lungmetastatic20p12.2Hs.70903ESTs652602AB023169lungmetastatic20p12.2Hs.7935BTB (POZ) domain containing 3653572Y00064lungmetastatic20p12.3Hs.2281chromogranin B (secretogranin 1)654582AI949781lungmetastatic20p13Hs.26802chromosome 20 open reading frame 97655594AF336127lungmetastatic20p13Hs.105607solute carrier family 4 sodium bicarbonatetransporter-like member 11656596AI096882lungmetastatic20p13Hs.135056chromosome 20 open reading frame 139657662AK000490prostateprimary1p31.2Hs.133260hypothetical protein FLJ20354658659AW271106prostateprimary1q22Hs.133294ESTs659660AI053741prostateprimary1q22Hs.133294ESTs660663AA830844prostateprimary1q23.2Hs.127310kinase interacting with leukemia-associatedgene (stathmin)661657AF326731prostateprimary1q23.3Hs.234545cell division cycle associated 1662661AB032931prostateprimary1q32.1Hs.5199HSPC150 protein similar to ubiquitin-conjugating enzyme663658U30872prostateprimary1q32.3Hs.77204centromere protein F 350/400 ka (mitosin)664684AI492879prostateprimary2p25.1Hs.75319ribonucleotide reductase M2 polypeptide665683N21131prostateprimary2q37.3Hs.42949hairy and enhancer of split 6 (Drosophila)666690BE407516prostateprimary5q13.2Hs.23960cyclin B1667691U70370prostateprimary5q31.1Hs.84136paired-like homeodomain transcription factor 1668692BE794699prostateprimary6p21.2Hs.284207hypothetical protein BC003515669694AI343467prostateprimary7p14.1Hs.28792Homo sapiens cDNA FLJ11041 fis clonePLACE1004405670695M13436prostateprimary7p14.1Hs.727inhibin beta A (activin A activin AB alphapolypeptide)671693AK023208prostateprimary7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)672698AI932328prostateprimary8p21.1Hs.104741T-LAK cell-originated protein kinase673697AA203476prostateprimary8q13.2Hs.252587pituitary tumor-transforming 1674696AI925583prostateprimary8q24.13Hs.222088hypothetical protein MGC5254675700BE544837prostateprimary9q33.2Hs.352417Homo sapiens Similar to RIKEN cDNA3321402G02 gene clone MGC: 23929IMAGE: 4807540 mRNA complete cds676699AI983261prostateprimary9q34.3Hs.323445ESTs Weakly similar to T2D3_HUMANTranscription initiation factor TFIID 135 kDasubunit (TAFII-135) (TAFII135)677664X05360prostateprimary10q21.2Hs.334562cell division cycle 2 G1 to S and G2 to M678665AI674163prostateprimary10q23.33Hs.14559hypothetical protein FLJ10540679666BE614410prostateprimary11q13.1Hs.23044similar to RIKEN cDNA 2610036L13680667U74612prostateprimary12p13.33Hs.239forkhead box M1681668R61322prostateprimary12q24.31Hs.204166Human clone 295 5cM region surroundinghepatocyte nuclear factor-1a/MODY3 mRNA682669L25876prostateprimary14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)683670U65410prostateprimary14q23.1Hs.79078MAD2 mitotic arrest deficient-like 1 (yeast)684671AL080146prostateprimary15q21.3Hs.194698cyclin B2685672D14657prostateprimary15q22.2Hs.81892KIAA0101 gene product686674AB018009prostateprimary16NULLHs.184601solute carrier family 7 (cationic amino acidtransporter y+ system) member 5687673AI819340prostateprimary16p13.3Hs.13561hypothetical protein MGC4692688678BE328850prostateprimary17q11.2Hs.348504hypothetical protein BC014072689679AF063308prostateprimary17q11.2Hs.16244mitotic spindle coiled-coil related protein690676AW003286prostateprimary17q21.31Hs.370428ESTs Moderately similar to TP2A_HUMANDNA topoisomerase II alpha isozyme[H. sapiens]691680AI375913prostateprimary17q21.31Hs.156346topoisomerase (DNA) II alpha 170 kDa692681L47276prostateprimary17q21.31NULLunknown693677BG165011prostateprimary17q23.2Hs.165909ESTs Weakly similar to hypothetical proteinFLJ20489 [Homo sapiens] [H. sapiens]694675BF056791prostateprimary17q23.3Hs.87507ESTs695682AA719022prostateprimary19q13.43Hs.288549ubiquitin UBF-fl696686D80008prostateprimary20p11.21Hs.36232KIAA0186 gene product697685AF098158prostateprimary20q11.1Hs.9329chromosome 20 open reading frame 1698688U73379prostateprimary20q13.12Hs.93002ubiquitin-conjugating enzyme E2C699687AF011468prostateprimary20q13.31Hs.250822serine/threonine kinase 6700701T77624prostateprimary21q22.13Hs.79375holocarboxylase synthetase (biotin-[proprionyl-Coenzyme A-carboxylase (ATP-hydrolysing)]ligase)701689AI381686prostateprimary22q13.2Hs.208912hypothetical protein MGC861702723AA630330prostatemetastatic1q21.2Hs.89545proteasome (prosome macropain) subunit betatype 4703771AW271106prostatemetastatic1q22Hs.133294ESTs704773AI690773prostatemetastatic1q22Hs.133294ESTs705803AI766666prostatemetastatic1q22Hs.374850apolipoprotein A-I binding protein706739AI249980prostatemetastatic1q23.2Hs.127310kinase interacting with leukemia-associatedgene (stathmin)707798AI015982prostatemetastatic1q23.3Hs.234545cell division cycle associated 1708745H62656prostatemetastatic1q24.3Hs.300893hypothetical protein MGC17528709753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported by BC007071710796U30872prostatemetastatic1q32.3Hs.77204centromere protein F 350/400 ka (mitosin)711794AA151971prostatemetastatic1q42.2Hs.334372chorionic somatomammotropin hormone 2712748AI971357prostatemetastatic3p21.32Hs.146170hypothetical protein FLJ22969713778W24316prostatemetastatic3q12.3Hs.173374endothelial and smooth muscle cell-derivedneuropilin-like protein714716AI338462prostatemetastatic3q26.1Hs.50758SMC4 structural maintenance ofchromosomes 4-like 1 (yeast)715717AB019987prostatemetastatic3q26.1Hs.50758SMC4 structural maintenance ofchromosomes 4-like 1 (yeast)716740AL119157prostatemetastatic3q26.32Hs.22941KIAA1363 protein717777BG170335prostatemetastatic3q26.32Hs.122579epithelial cell transforming sequence 2oncogene718704AI968388prostatemetastatic3q26.33NULLunknown719724AA194529prostatemetastatic3q28Hs.74619proteasome (prosome macropain) 26S subunitnon-ATPase 2720760BE256479prostatemetastatic5p14.3Hs.79037heat shock 60 kDa protein 1 (chaperonin)721705AI750154prostatemetastatic5p15.1NULLunknown722711U96131prostatemetastatic5p15.33Hs.6566thyroid hormone receptor interactor 13723787M25753prostatemetastatic5q13.2Hs.23960cyclin B1724758AI369840prostatemetastatic6p21.1Hs.374582Homo sapiens cDNA FLJ11842 fis cloneHEMBA1006652 weakly similar to 60SRIBOSOMAL PROTEIN L7725804AK023208prostatemetastatic7p14.2Hs.62180anillin actin binding protein (scraps homologDrosophila)726752AI910524prostatemetastatic7p15.3Hs.87385hypothetical protein BC012331727721L07493prostatemetastatic7p21.3Hs.1608replication protein A3 14 kDa728730AL582836prostatemetastatic7q21.3Hs.137476paternally expressed 10729770AI922470prostatemetastatic7q21.3Hs.370106ESTs Highly similar to asparagine synthetase[Homo sapiens] [H. sapiens]730726L37127prostatemetastatic7q22.1Hs.80475polymerase (RNA) II (DNA directed)polypeptide J 13.3 kDa731736AA193396prostatemetastatic7q31.2Hs.285754met proto-oncogene (hepatocyte growth factorreceptor)732768AI679933prostatemetastatic7q33Hs.369347ESTs Weakly similar to hypothetical proteinFLJ20378 [Homo sapiens] [H. sapiens]733763AI571298prostatemetastatic8NULLHs.343589exosome component Rrp41734732AA191576prostatemetastatic8q12.1Hs.9614nucleophosmin (nucleolar phosphoprotein B23numatrin)735801AW001796prostatemetastatic8q12.3Hs.283664aspartate beta-hydroxylase736729AA203476prostatemetastatic8q13.2Hs.252587pituitary tumor-transforming 1737795AI525903prostatemetastatic8q13.3Hs.118554CGI-83 protein738710AA995715prostatemetastatic8q21.11Hs.184693transcription elongation factor B (SIII)polypeptide 1 (15 kDa elongin C)739782BE409290prostatemetastatic8q22.3Hs.273344DKFZP564O0463 protein740788AA584310prostatemetastatic8q22.3Hs.283713collagen triple helix repeat containing 1741769BF109660prostatemetastatic8q23.1Hs.127286ESTs Moderately similar to leucine-richneuronal protein [Homo sapiens] [H. sapiens]742789AI802955prostatemetastatic8q23.2Hs.195870chronic myelogenous leukemia tumor antigen66743737AL117612prostatemetastatic8q24.12Hs.76550mal T-cell differentiation protein 2744756AI880004prostatemetastatic8q24.22Hs.356036Homo sapiens mRNA cDNA DKFZp666E036(from clone DKFZp666E036)745784AI023398prostatemetastatic8q24.22Hs.10669development and differentiation enhancingfactor 1746706AA527374prostatemetastatic8q24.23NULLunknown747702AF067656prostatemetastatic10q21.1Hs.42650ZW10 interactor748799AF154332prostatemetastatic10q21.2Hs.334562cell division cycle 2 G1 to S and G2 to M749802BC006121prostatemetastatic10q22.1Hs.117062apoptosis-inducing factor (AIF)-homologousmitochondrion-associated inducer of death750728K03226prostatemetastatic10q22.2Hs.77274plasminogen activator urokinase751805U90339prostatemetastatic10q22.2Hs.94382adenosine kinase752725AI198535prostatemetastatic10q22.3Hs.89463potassium large conductance calcium-activated channel subfamily M alpha member 1753734N27428prostatemetastatic10q23.31Hs.240M-phase phosphoprotein 1754751AI674163prostatemetastatic10q23.33Hs.14559hypothetical protein FLJ10540755718BE614410prostatemetastatic11q13.1Hs.23044similar to RIKEN cDNA 2610036L13756761BG251266prostatemetastatic11q13.1Hs.283565FOS-like antigen 1757733AA621983prostatemetastatic11q13.3Hs.116051myeloma overexpressed gene (in a subset oft(11 14) positive multiple myelomas)758722U82984prostatemetastatic12q13.12Hs.23900Rac GTPase activating protein 1759747AF091087prostatemetastatic12q13.12Hs.206501hypothetical protein from clone 643760754AI936946prostatemetastatic12q13.12Hs.121973Homo sapiens clone MGC: 20874IMAGE: 4547239 mRNA complete cds761707AL118633prostatemetastatic12q13.13Hs.151678UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6)762741X81420prostatemetastatic12q13.13Hs.32952keratin hair basic 1763762D79987prostatemetastatic12q13.13Hs.153479extra spindle poles like 1 (S. cerevisiae)764727AF025840prostatemetastatic14q21.2Hs.99185polymerase (DNA directed) epsilon 2 (p59subunit)765744AA648933prostatemetastatic14q21.2Hs.374811hypothetical protein MGC20689766749BC006117prostatemetastatic14q21.3Hs.222021hypothetical protein FLJ12618767750AI924794prostatemetastatic14q21.3Hs.27931hypothetical protein FLJ10607 similar toglucosamine-phosphate N-acetyltransferase768776AW268365prostatemetastatic14q21.3Hs.25740ERO1-like (S. cerevisiae)769780D13633prostatemetastatic14q22.1Hs.77695Drosophila discs large-1 tumor supressor-like770785L25876prostatemetastatic14q22.1Hs.84113cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)771766AI417084prostatemetastatic14q22.2Hs.301231ESTs Weakly similar to PSA3_HUMANProteasome subunit alpha type 3 (Proteasomecomponent C8) (Macropain772735J04031prostatemetastatic14q23.1Hs.172665methylenetetrahydrofolate dehydrogenase(NADP+ dependent) methenyltetrahydrofolatecyclohydrolase formyltetrahydrofolatesynthetase773738U65410prostatemetastatic14q23.1Hs.79078MAD2 mitotic arrest deficient-like 1 (yeast)774731AA926959prostatemetastatic14q32.12Hs.77550p53-regulated DDA3775764AL080102prostatemetastatic14q32.2Hs.334810eukaryotic translation initiation factor 5776779BF000332prostatemetastatic14q32.2Hs.7720dynein cytoplasmic heavy polypeptide 1777786AI525727prostatemetastatic14q32.2Hs.38205cyclin-dependent kinase 2-interacting protein778800AI761729prostatemetastatic14q32.2Hs.12908CDC42 binding protein kinase beta (DMPK-like)779746T65554prostatemetastatic14q32.31Hs.317821hypothetical protein MGC13251780755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens clone MGC: 16771IMAGE: 3907551 mRNA complete cds781797AI684508prostatemetastatic14q32.31Hs.34045cell division cycle associated 4782715U81800prostatemetastatic17NULLHs.85838solute carrier family 16 (monocarboxylic acidtransporters) member 3783774AI292123prostatemetastatic17NULLHs.201390ESTs784743AI458014prostatemetastatic17q22Hs.283558hypothetical protein PRO1855785775AA564822prostatemetastatic17q22Hs.298564ESTs786767BG165011prostatemetastatic17q23.2Hs.165909ESTs Weakly similar to hypothetical proteinFLJ20489 [Homo sapiens] [H. sapiens]787742U28386prostatemetastatic17q24.3Hs.159557karyopherin alpha 2 (RAG cohort 1 importinalpha 1)788713K02581prostatemetastatic17q25.3Hs.105097thymidine kinase 1 soluble789719AA312511prostatemetastatic17q25.3Hs.273307signal recognition particle 68 kDa790759AI525822prostatemetastatic17q25.3Hs.109706hematological and neurological expressed 1791772AI733461prostatemetastatic18p11.22Hs.127716ESTs792783AB000277prostatemetastatic18p11.31Hs.75814discs large (Drosophila) homolog-associatedprotein 1793712X02308prostatemetastatic18p11.32Hs.82962thymidylate synthetase794709M91670prostatemetastatic19q13.42Hs.174070ubiquitin carrier protein795708AA719022prostatemetastatic19q13.43Hs.288549ubiquitin UBF-fl796792AI761506prostatemetastatic20p13Hs.274422chromosome 20 open reading frame 27797793H06350prostatemetastatic20p13Hs.135056chromosome 20 open reading frame 139798720AF011468prostatemetastatic20q13.31Hs.250822serine/threonine kinase 6799714AW016409prostatemetastatic20q13.33Hs.235782solute carrier family 21 (organic aniontransporter) member 12800765X70940prostatemetastatic20q13.33Hs.2642eukaryotic translation elongation factor 1 alpha 2801791AI652030prostatemetastatic21q22.11Hs.49932chromosome 21 open reading frame 45802703AI861913prostatemetastatic21q22.3Hs.143638WD repeat domain 4803757AA577678prostatemetastatic21q22.3Hs.282961Homo sapiens cDNA FLJ35467 fis cloneSMINT2005624804781AI860822prostatemetastatic21q22.3Hs.110757DNA segment on chromosome 21 (unique)2056 expressed sequence805790AI983544prostatemetastatic21q22.3Hs.126522chromosome 21 open reading frame 70806120R62346breastmetastatic1q23.2NULLunknownProtein807120R62346breastmetastatic1q23.2NULLunknownProtein808120R62346breastmetastatic1q23.2NULLunknownProtein809120R62346breastmetastatic1q23.2NULLunknownProtein810120R62346breastmetastatic1q23.2NULLunknownProtein811120R62346breastmetastatic1q23.2NULLunknownTranscript812120R62346breastmetastatic1q23.2NULLunknownTranscript813120R62346breastmetastatic1q23.2NULLunknownTranscript814120R62346breastmetastatic1q23.2NULLunknownTranscript815120R62346breastmetastatic1q23.2NULLunknownTranscript816120R62346breastmetastatic1q23.2NULLunknownTranscript817120R62346breastmetastatic1q23.2NULLunknownTranscript818197AA663786breastmetastatic3p21.31NULLunknownTranscript819194AI962335breastmetastatic3p24.3Hs.196042ESTsTranscript820227W25552breastmetastatic9q34.3Hs.212613hypothetical protein FLJ36779Protein821227W25552breastmetastatic9q34.3Hs.212613hypothetical protein FLJ36779Transcript82277AI962335breastprimary3p24.3Hs.196042ESTsTranscript823101W25552breastprimary9q34.3Hs.212613hypothetical protein FLJ36779Protein824101W25552breastprimary9q34.3Hs.212613hypothetical protein FLJ36779Transcript825334AI962335colonmetastatic3p24.3Hs.196042ESTsTranscript826393W25552colonmetastatic9q34.3Hs.212613hypothetical protein FLJ36779Protein827393W25552colonmetastatic9q34.3Hs.212613hypothetical protein FLJ36779Transcript828301AI962335colonprimary3p24.3Hs.196042ESTsTranscript829328W25552colonprimary9q34.3Hs.212613hypothetical protein FLJ36779Protein830328W25552colonprimary9q34.3Hs.212613hypothetical protein FLJ36779Transcript831527AK022113lungprimary1p31.3Hs.301858Homo sapiens cDNA FLJ13017 fis,Transcriptclone NT2RP3000628832527AK022113lungprimary1p31.3Hs.301858Homo sapiens cDNA FLJ13017 fis,Transcriptclone NT2RP3000628833458AA383208lungprimary5p15.1Hs.125249ESTsProtein834458AA383208lungprimary5p15.1Hs.125249ESTsTranscript835519C00851lungprimary5p13.2Hs.144264ESTs, Weakly similar to hypotheticalTranscriptprotein FLJ20837 [Homo sapiens][H. sapiens]836505AA904882lungprimary8q22.3Hs.130107ESTsTranscript837529AK024242lungprimary8q21.11Hs.296753Homo sapiens cDNA FLJ14180 fis,Transcriptclone NT2RP2003799838529AK024242lungprimary8q21.11Hs.296753Homo sapiens cDNA FLJ14180 fis,Proteinclone NT2RP2003799839555AF232217lungprimary8q13.3NULLunknownTranscript840513AI146765lungprimary18p11.31Hs.373550ESTsTranscript841753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byProteinBC007071842753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byProteinBC007071843753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byProteinBC007071844753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byProteinBC007071845753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byProteinBC007071846753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071847753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071848753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byProteinBC007071849753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071850753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071851753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071852753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071853753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071854753N29457prostatemetastatic1q31.1Hs.117305hypothetical gene supported byTranscriptBC007071855705AI750154prostatemetastatic5p15.1NULLunknownProtein856705AI750154prostatemetastatic5p15.1NULLunknownTranscript857755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds858755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds859755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds860755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771Protein0IMAGE: 3907551, mRNA, complete cds861755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds862755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds863755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds864755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds865755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds866755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds867755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds868755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds869755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds870755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds871755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771Protein0IMAGE: 3907551, mRNA, complete cds872755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds873755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds874755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds875755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds876755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds877755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds878755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds879755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds880755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds881755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds882755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds883755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds884755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds885755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds886755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds887755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds888755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds889755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771ProteinIMAGE: 3907551, mRNA, complete cds890755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds891755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds892755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds893755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds894755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds895755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds896755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds897755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds898755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds899755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds900755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds901755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds902755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds903755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds904755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds905755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds906755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds907755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds908755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds909755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds910755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds911755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds912755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds913755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds914755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds915755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds916755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds917755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds918755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds919755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds920755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds921755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds922755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds923755H04885prostatemetastatic14q32.31Hs.72363Homo sapiens, clone MGC: 16771TranscriptIMAGE: 3907551, mRNA, complete cds


Claims
  • 1-4. (canceled)
  • 5. A method for diagnosing cancer or a pre-cancerous condition in a mammal, comprising: (a) obtaining a cell or tissue sample from a mammal suspected of having cancer or a pre-cancerous condition and determining for said sample the gene copy number of a gene of Table 1; (b) comparing said gene copy number of step (a) to the gene copy number of the same gene from a sample of a corresponding cell or tissue from a mammal of the same species not having cancer of the type being diagnosed whereby a higher gene copy number determined in step (a) relative to that in step (b) indicates the presence of a cancer or pre-cancerous condition in the mammal of step (a) and results in a diagnosis of cancer or a pre-cancerous condition in said mammal.
  • 6. The method of claim 5 wherein said mammal is a human patient.
  • 7. The method of claim 5 wherein said cancer is a member selected from breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.
  • 8. The method of claim 5 wherein the gene of Table 1 is a gene that encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 9. A method of inhibiting cancer, or a pre-cancerous condition, in a mammalian cell, comprising contacting said cell with a molecule that inhibits function of a gene of Table 1.
  • 10. The method of claim 9 wherein said gene of Table 1 is a gene that encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 11. The method of claim 9 wherein said molecule inhibits gene function by binding to said gene.
  • 12. The method of claim 9 wherein said molecule inhibits gene function by binding to an RNA encoded by said gene.
  • 13. The method of claim 9 wherein said molecule inhibits gene function by binding to polypeptide encoded by said gene.
  • 14. The method of claim 9 wherein said molecule is a member selected from an antisense DNA, an antisense RNA, a ribozyme and an siRNA.
  • 15. The method of claim 9 wherein said cancer is a member selected from breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.
  • 16. The method of claim 9 wherein said contacting occurs in vivo.
  • 17. A method for identifying an agent having therapeutic activity in a human patient in need of said therapeutic activity, comprising: (a) determining in a sample from a patient the level of a gene product encoded by a gene of Table 1 prior to administering a test compound to said patient; (b) administering said test compound to said patient; (c) determining in a sample from said patient the level of a gene product encoded by the same the gene as in step (a) wherein a decrease in the level of said gene product in step (c) relative to step (a) identifies said test compound as an agent having therapeutic activity.
  • 18. The method of claim 17 wherein said therapeutic activity is anticancer activity.
  • 19. The method of claim 17 wherein said cancer is a member selected from breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer and kidney cancer.
  • 20. The method of claim 17 wherein said gene product is an RNA.
  • 21. The method of claim 17 wherein said gene product is a polypeptide.
  • 22. The method of claim 21 wherein said determination of said polypeptide is a determination of an enzyme activity.
  • 23. The method of claim 17 wherein said gene of Table 1 is a gene that encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 24. The method of claim 17 wherein said molecule is a member selected from an antisense DNA, an antisense RNA, a ribozyme and an siRNA.
  • 25. A method for identifying an antineoplastic agent, comprising: (a) contacting a test compound with a cell that expresses a gene of Table 1; and (b) determining a change in gene expression as a result of said contacting; whereby said change in said gene expression identifies said test compound as an antineoplastic agent.
  • 26-27. (canceled)
  • 28. The method of claim 25 wherein said gene of Table 1 encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 29. The method of claim 25 wherein said molecule is a member selected from an antisense DNA, an antisense RNA, ribozyme, an siRNA, a small organic molecule and an antibody.
  • 30. A method for determining the cancerous status of a cell, comprising determining elevated expression in said cell of a gene of Table 1 wherein elevated expression of said gene indicates that said cell is cancerous.
  • 31. (canceled)
  • 32. The method of claim 30 wherein said gene of Table 1 encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 33. A method for identifying a compound as an anti-neoplastic agent, comprising: (a) contacting a test compound with a polypeptide encoded by a gene of Table 1, (b) determining a change in a biological activity of said polypeptide due to said contacting, wherein a change in activity identifies said test compound as an agent having antineoplastic activity.
  • 34. The method of claim 33 wherein said gene of Table encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 35. (canceled)
  • 36. The method of claim 33 wherein said biological activity is an enzyme activity.
  • 37-55. (canceled)
  • 56. The method of claim 33 wherein said polypeptide is contained in a cell.
  • 57. The method of claim 33 wherein said molecule is a member selected from antisense DNA, an antisense RNA, a ribozyme, an siRNA, a small organic molecule and an antibody.
  • 58. The method of claim 57 wherein said antibody is specific for a polypeptide comprising an amino acid sequence of SEQ ID NO: 806 -854.
  • 59-61. (canceled)
  • 62. A method for treating cancer comprising contacting a cancerous cell with an agent first identified as having gene modulating activity using the method of claim 25, 33, or 58 and in an amount effective to cause a reduction in cancerous activity of said cell.
  • 63-66. (canceled)
  • 67. A method for treating cancer comprising contacting a cancerous cell with an agent having affinity for an expression product of a gene of Table 1 and in an amount effective to cause a reduction in cancerous activity of said cell.
  • 68. The method of claim 67 wherein said expression product is a polypeptide.
  • 69. The method of claim 67 wherein said molecule is a member selected from antisense DNA, an antisense RNA, a ribozyme, an siRNA, a small organic molecule and an antibody.
  • 70. The method of claim 69 wherein said antibody is specific for a polypeptide comprising an amino acid sequence selected from SEQ ID NO: 806-854.
  • 71. A method for monitoring the progress of cancer therapy in a patient comprising monitoring in a patient undergoing cancer therapy the expression of a gene of Table 1.
  • 72. The method of claim 71 wherein said gene encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 73-74. (canceled)
  • 75. A method for determining the likelihood of success of cancer therapy in a patient, comprising monitoring in a patient undergoing cancer therapy the expression of a gene of Table 1 wherein a decrease in said expression prior to completion of said cancer therapy is indicative of a likelihood of success of said cancer therapy.
  • 76. The method of claim 75 wherein said gene encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
  • 77-78. (canceled)
  • 79. A method for producing test data with respect to the anti-neoplastic activity of a compound comprising: (a) identifying a test compound as having anti-neoplastic activity using a method of claim 25;(b) producing test data with respect to the anti-neoplastic activity of said test compound sufficient to identify the chemical structure of said test compound.
  • 80. A method for producing test data with respect to the anti-neoplastic activity of a compound comprising: (a) identifying a test compound as having anti-neoplastic activity using a method of claim 33;(b) producing test data with respect to the anti-neoplastic activity of said test compound sufficient to identify the chemical structure of said test compound.
  • 81. A method for determining the progress of a treatment for cancer in a patient afflicted therewith, following commencement of a cancer treatment on said patient, comprising: (a) determining in said patient a change in expression of one or more genes of Table 1; and (b) determining a change in expression of said gene compared to expression of said one or more determined genes prior to said cancer treatment; wherein said change in expression indicates progress of said treatment thereby determining the progress of said treatment.
  • 82. The method of claim 81 wherein said change in expression is a decrease in expression and said decrease indicates success of said treatment.
  • 83. The method of claim 81 wherein said gene encodes the same gene product as a polynucleotide of SEQ ID NO: 1-805 and 855-923.
Parent Case Info

This application claims priority of U.S. Provisional Application Ser. No. 60/462,895, filed 15 Apr. 2003, the disclosure of which is hereby incorporated by reference in its entirety.

PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/US04/09289 4/15/2004 WO 11/21/2006
Provisional Applications (1)
Number Date Country
60462895 Apr 2003 US