Claims
- 1. An isolated human nucleic acid encoding a nevoid basal cell carcinoma syndrome (NBCCS) (PTC) protein, wherein said nucleic acid specifically hybridizes, under stringent conditions, to a second nucleic acid consisting of a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59, in the presence of a human genomic library under stringent conditions.
- 2. The isolated human nucleic acid of claim 1, wherein said isolated nucleic acid is at least 40 nucleotides in length.
- 3. The nucleic acid of claim 1, wherein said isolated nucleic acid is amplified from a genomic library using any of the primer pairs provided in Table 2.
- 4. The nucleic acid of claim 1, wherein said isolated nucleic acid is identified by specific hybridization with the nucleic acids of claim 3 under stringent conditions.
- 5. The nucleic acid of claim 1, wherein said nucleic acid is a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 6. The nucleic acid of claim 1, wherein said nucleic acid includes one or more mutations compared to a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 7. The nucleic acid of claim 6, wherein the mutation or mutations is selected from the group consisting of Exon 5 693 insC, Exon 17 2988 del8bp, Exon 17 3014 insA, Exon 21 3538 delG, Exon 22 G4302T, Exon 12 1711insC, Exon 12 1639insA, Exon 16 2707delC, and Intron 17 3157-2→G.
- 8. The nucleic acid of claim 6, wherein the mutation is a nonsense mutation.
- 9. The nucleic acid of claim 6, wherein the mutation is a frameshift mutation.
- 10. The nucleic acid of claim 9, wherein the mutation is selected from the group consisting of 244delCT, 217insA, 464insAC, 693insC, 804del37, 877delG, 929delC, 1370del76, 1393insTGCC, 1444del6, 1497dup8, 1639insA, 1711insC, 2183delTC, 2320insA, 2392delA, 2574delA, 2583delC, 2596complex, 2707delC, 2748insC, 2749dup7, 2988del8bp, 3014insA, 3352delAT, and 3538delG.
- 11. The nucleic acid of claim 6, wherein the mutation is a missense mutation.
- 12. The nucleic acid of claim 11, wherein the mutation is selected from the group consisting of C391 T, G1148A, G1368A, G]525T, C2050T, C2050T, C2068T, C3015A, G3193C, and G4302T.
- 13. The nucleic acid of claim 6, wherein the mutation alters mRNA splicing.
- 14. The nucleic acid of claim 13, wherein the mutation is selected from the group consisting of A1055-2C, 3157-2A→G, and 1493-8ins21.
- 15. The nucleic acid of claim 1, wherein the nucleic acid further comprises a recombinant vector.
- 16. An isolated human nevoid basal cell carcinoma syndrome (NBCCS) (PTC) nucleic acid, wherein said nucleic acid encodes a polypeptide subsequence of at least 10 contiguous amino acid residues of a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59, or conservative substitutions of said polypeptide subsequence.
- 17. The nucleic acid of claim 16, wherein said polypeptide subsequence is at least 50 amino acid residues in length.
- 18. The nucleic acid of claim 17, wherein said polypeptide is the polypeptide sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 19. The nucleic acid of claim 16, wherein the nucleic acid further comprises a recombinant vector.
- 20. An isolated nucleic acid encoding a human nevoid basal cell carcinoma (NBCCS) (PTC) polypeptide comprising at least 10 contiguous amino acids from a polypeptide sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59, wherein:
said polypeptide, when presented as an antigen, elicits the production of an antibody which specifically binds to a polypeptide sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59; and said polypeptide does not bind to antisera raised against a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59 which has been fully immunosorbed with a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 21. The nucleic acid of claim 20, wherein said nucleic acid hybridizes to a clone of the human PTC gene present in a human genomic library under stringent conditions.
- 22. The nucleic acid of claim 23, wherein the nucleic acid further comprises a recombinant vector.
- 24. An isolated NBCCS (PTC) polypeptide, said polypeptide comprising a subsequence of at least 10 contiguous amino acids of a polypeptide encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59, or conservative substitutions of said polypeptide subsequence.
- 25. The polypeptide of claim 24, wherein said polypeptide comprises a subsequence of at least 50 contiguous amino acids encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59, or conservative substitutions of said polypeptide subsequence.
- 26. The polypeptide of claim 24, wherein said polypeptide is a polypeptide encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 27. An isolated NBCCS (PTC) polypeptide, said polypeptide comprising at least 10 contiguous amino acids from a polypeptide sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59, wherein:
said polypeptide, when presented as an antigen, elicits the production of an antibody which specifically binds to a polypeptide encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59; and said polypeptide does not bind to antisera raised against a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59 which has been fully immunosorbed with a polypeptide encoded by a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 28. The isolated polypeptide of claim 27, wherein said polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 29. An antibody which specifically binds a polypeptide comprising at least 10 contiguous amino acids from a polypeptide encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59 wherein:
said polypeptide, when presented as an antigen, elicits the production of an antibody which specifically binds to a polypeptide encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59; and said polypeptide does not bind to antisera raised against a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59 which has been fully immunosorbed with a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 30. The antibody of claim 29, wherein said antibody is monoclonal.
- 31. A recombinant cell expressing the antibody of claim 29.
- 32. A method of detecting a predisposition to nevoid basal cell carcinoma syndrome (NBCCS) or to a basal cell carcinoma, said method comprising the steps of
i) providing a biological sample of said organism; and ii) detecting a human NBCCS (PTC) gene or gene product in said sample.
- 33. The method of claim 32, wherein said detecting comprises detecting the presence or absence of a NBCCS nucleic acid.
- 34. The method of claim 33, wherein said detecting comprises a hybridization assay.
- 35. The method of claim 33, wherein said detecting comprises detecting an abnormal NBCCS nucleic acid.
- 36. The method of claim 35, wherein the abnormal NBCCS nucleic acid includes one or more mutations compared to a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 58, and SEQ. ID NO: 59.
- 37. The method of claim 36, wherein the mutation is selected from the group consisting of a missense mutation, a nonsense mutation, a frameshift mutation, and a splice site mutation.
- 38. The method of claim 32, wherein said detecting comprises sequencing said human NBCCS gene or gene product.
- 39. The method of claim 32, wherein said detecting comprises detecting an NBCCS polypeptide.
- 40. The method of claim 39, wherein said detecting comprises an immunoassay.
- 41. A method of treating nevoid basal cell carcinoma syndrome (NBCCS) in a mammal, said method comprising transfecting cells of said mammal with vector expressing a nevoid basal cell carcinoma syndrome (NBCCS) polypeptide.
- 42. A method of mitigating a symptom of nevoid basal cell carcinoma syndrome or a basal cell carcinoma in an organism, said method comprising administering to said organism a therapeutically effective dose of a composition comprising a NBCCS (PTC) polypeptide and a pharmacological excipient.
- 43. A pharmacological composition comprising a pharmaceutically acceptable carrier and a molecule selected from the group consisting of consisting of a vector encoding an NBCCS polypeptide or subsequence thereof, an NBCCS polypeptide or subsequence thereof, and an anti-NBCCS antibody.
- 44. A kit for the detection of a NBCCS (PCT) gene or polypeptide, said kit comprising a container containing a molecule selected from the group consisting of an NBCCS polypeptide or subsequence thereof, and an anti-NBCCS antibody.
Priority Claims (2)
Number |
Date |
Country |
Kind |
PO0011 |
May 1996 |
AU |
|
PO0363 |
Jun 1996 |
AU |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. application Ser. No. 60/017,906, filed on May 17, 1996 and U.S. application Ser. No: 60/019765, filed on Jun. 14, 1996, both of which are herein incorporated by reference for all purposes.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60017906 |
May 1996 |
US |
|
60019765 |
Jun 1996 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
08857636 |
May 1997 |
US |
Child |
10302279 |
Nov 2002 |
US |