Tumor suppressor designated TS10Q23.3

• US 20070054333A1
• Filed: 10/30/2006
• Published: 03/08/2007
• Est. Priority Date: 01/30/1997
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Myriad Genetics
• Inventors: Steck, Peter, Pershouse, Mark, Yung, Alfred, Jasser, Samar, Tavtigian, Sean
• Granted Patent: US 7,732,576 B2
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C12N 2799/021 for the expression of a heterologous nucleic acid
• CPC Class Codes: C12N 9/16 acting on ester bonds (3.1)
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: C12Q 2600/172 Haplotypes
• CPC Class Codes: G01N 2333/916 acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57434 of prostate
• CPC Class Codes: G01N 33/57496 involving intracellular compounds

Abstract

A specific region of chromosome 10 (10q23.3) has been implicated by series of studies to contain a tumor suppressor gene involved in gliomas, as well as a number of other human cancers. One gene within this region was identified, and the corresponding coding region of the gene represents a novel 47 kD protein. A domain of this product has an exact match to the conserved catalytic domain of protein tyrosine phosphatases, indicating a possible functional role in phosphorylation events. Sequence analyses demonstrated the a number of exons of the gene were deleted in tumor cell lines used to define the 10q23.3 region, leading to the classification of this gene as a tumor suppressor. Further analyses have demonstrated the presence of a number of mutations in the gene in both glioma and prostate carcinoma cells. Methods for diagnosing and treating cancers related to this tumor suppressor, designated as TS10q23.3, also are disclosed.

Claims

1. A method for determining the level of expression of a PTEN protein or transcript in a sample comprising (i) obtaining a tissue or body fluid sample from a subject;

and (ii) determining the level of a PTEN protein or transcipt in said sample, wherein the amino acid sequence of said PTEN protein has the amino acid sequence set forth in SEQ ID NO;

2.

2. The method of claim 1, wherein said sample comprises a cancer cell.

3. The method of claim 1, wherein said sample is a tumor sample.

4. The method of claim 3, wherein said tumor sample is chosen from brain, lung, liver, spleen, kidney, lymph node, small intestine, pancreas, blood cells, colon, stomach, breast, endometrial, prostate, testicle, ovary, skin, head and neck, esophagus, bone marrow, and blood tumor sample.

5. The method of claim 2, wherein said cancer cell sample is chosen from brain, lung, liver, spleen, kidney, lymph node, small intestine, pancreas, blood cells, colon, stomach, breast, endometrial, prostate, testicle, ovary, skin, head and neck, esophagus, bone marrow, and blood cancer cell sample.

6. The method of claim 1, wherein said sample is obtained from a prostate tumor or cancer cell.

7. The method of claim 1, wherein said sample is obtained from a brain tumor or cancer cell.

8. The method of claim 1, wherein said sample is obtained from a lung tumor or cancer cell.

9. The method of claim 1, wherein said sample is obtained from an endometrial tumor or cancer cell.

10. The method of claim 1, wherein said sample is obtained from a colon tumor or cancer cell.

11. The method of claim 1, wherein said sample is obtained from a head and neck tumor or cancer cell.

12. The method of claim 1, wherein said sample is obtained from a breast tumor or cancer cell.

13. The method of claim 1, wherein said determining comprises assaying for a nucleic acid in said sample wherein said nucleic acid encodes said PTEN.

14. The method of claim 13, wherein said assaying comprises a quantitative PCR assay.

15. The method of claim 13, further comprising subjecting the sample to conditions suitable for amplifying a portion of said nucleic acid.

16. The method of claim 13, wherein said method comprises selectively amplifying said nucleic acid.

17. The method of claim 14, wherein said quantitative PCR assay comprises using an internal standard or an external standard.

18. The method of claim 13, wherein said sample is chosen is obtained from a tissue sample or a fluid sample.

19. The method of claim 13, wherein said sample is a tumor sample or a cancer cell sample.

20. The method of claim 19, wherein said tumor sample is chosen from brain, lung, liver, spleen, kidney, lymph node, small intestine, pancreas, blood cells, colon, stomach, breast, endometrial, prostate, testicle, ovary, skin, head and neck, esophagus, bone marrow, and blood tumor sample.

21. The method of claim 20, wherein said cancer cell sample is chosen from brain, lung, liver, spleen, kidney, lymph node, small intestine, pancreas, blood cells, colon, stomach, breast, endometrial, prostate, testicle, ovary, skin, head and neck, esophagus, bone marrow, and blood cancer cell sample.

22. The method of claim 13, wherein said sample is obtained from a prostate tumor or cancer cell.

23. The method of claim 13, wherein said sample is obtained from a brain tumor or cancer cell.

24. The method of claim 13, wherein said sample is obtained from a lung tumor or cancer cell.

25. The method of claim 13, wherein said sample is obtained from an endometrial tumor or cancer cell.

26. The method of claim 13, wherein said sample is obtained from a colon tumor or cancer cell.

27. The method of claim 13, wherein said sample is obtained from a head and neck tumor or cancer cell.

28. The method of claim 13, wherein said sample is obtained from a breast tumor or cancer cell.

29. The method of claim 1, wherein said determining step comprises contacting said sample with an antibody that binds immunologically to said protein.

30. The method of claim 29, wherein said antibody is a monoclonal antibody.

31. The method of claim 1, wherein said determining step comprises immunohistochemical detection of said protein in tissue sections.

32. The method of claim 29, wherein said tissue section is from a tumor sample.

33. The method of claim 32, wherein said tumor sample is selected from brain, lung, liver, spleen, kidney, lymph node, small intestine, pancreas, blood cells, colon, stomach, breast, endometrial, prostate, testicle, ovary, skin, head and neck, esophagus, bone marrow, and blood cancer tumors.

34. The method of claim 32, wherein said tumor sample is selected from brain, lung, colon, stomach, breast, endometrial, prostate, and head and neck tumor sample.

35. The method of claim 32, wherein said tumor sample is a brain cancer tumor sample.

36. The method of claim 32, wherein said tumor sample is a lung cancer tumor sample.

37. The method of claim 32, wherein said tumor sample is a colon cancer tumor sample.

38. The method of claim 32, wherein said tumor sample is a breast cancer tumor sample.

39. The method of claim 32, wherein said tumor sample is a prostate cancer tumor sample.

40. The method of claim 32, wherein said tumor sample is an endometrial cancer tumor sample.

41. The method of claim 32, wherein said tumor sample is a head and neck cancer tumor sample.

42. The method of claim 1, wherein said determining step comprises comparing the expression of PTEN in a cancer sample with the expression of PTEN in a non-cancer sample.

43. The method of claim 29, wherein said cancer is breast tissue or cells.

44. The method of claim 43, wherein said sample is a tissue or fluid sample.

45. The method of claim 43, wherein said antibody is a monoclonal antibody.

46. The method of claim 43, wherein said monoclonal antibody comprises a detectable label.

47. The method of claim 43, wherein said detectable label is selected from a fluorescent label, a chemiluminescent label, a radiolabel, and an enzyme label.

48. A method for detecting an alteration in two or more tumor suppressors or oncogenes, said method comprising:

obtaining a sample; and

evaluating PTEN expression and one or more other tumor suppressors or oncogenes.

49. The method of claim 48, wherein said one or more other tumor suppressor or oncogenes are chosen from EGFR, p53, p16, Rb, TGF-alpha, N-myc, DCC, BRCA1, p21, Rb, APC, DCC, NF-1, NF-2, BRCA2, WT-1, MEN-I, MEN-II, BRCA1, VHL, FCC, MCC, ras, myc, neu, raf, erb, src, fms, jun, trk, ret, gsp, hst, bcl, and abL.

50. The method of claim 48 wherein said evaluating comprises assaying said one or more other tumor suppressors or oncogenes with one or more methods chosen from DNA sequence analysis, quantitative PCR, copy number analysis, FISH, and detection with an antibody.

61. A method for determining the level of expression of a PTEN protein or transcript, said method comprising determining the level of a PTEN protein or transcript in a sample obtained from a subject, wherein said PTEN has the amino acid sequence set forth in SEQ ID NO:

2.