Claims
- 1. A method of diagnosing a predisposition to cancer in a subject comprising:
a. obtaining a nucleic acid sample from the subject; and b. determining whether one or more of the subject's Ku70 alleles or regulatory regions to those alleles are deleted or different from the wild type so as to reduce or eliminate the subject's expression of polypeptide having tumor suppressor activity.
- 2. The method of claim 1, wherein the cancer is T-cell lymphoma.
- 3. The method of claim 1, wherein the cancer is B-cell lymphoma.
- 4. The method of claim 1, wherein the cancer is neuroblastoma.
- 5. The method of claim 1, wherein the regulatory region is a promoter.
- 6. The method of claim 1, wherein the determining of step b comprises generating a polypeptide encoded by one or more of the subject's Ku70 alleles and comparing the resulting polypeptide to a wild type Ku70 polypeptide.
- 7. The method of claim 1, wherein the nucleic acid sample is obtained from the subject's blood.
- 8. A method of diagnosing a predisposition to cancer in a subject comprising: determining the level of Ku70 expression in the subject.
- 9. The method of claim 8, wherein the cancer is T-cell lymphoma.
- 10. The method of claim 8, wherein the cancer is B-cell lymphoma.
- 11. The method of claim 8, wherein the cancer is neuroblastoma.
- 12. The method of claim 8, wherein the level of Ku70 expression is determined based upon the level of Ku70 mRNA in the subject.
- 13. The method of claim 8, wherein the level of Ku70 expression is determined based upon the level of Ku70 polypeptide in the subject.
- 14. The method of claim 8, wherein zero or reduced Ku70 expression indicates a predisposition to cancer.
- 15. A method of diagnosing a predisposition to cancer in a subject comprising: determining the subcellular localization of Ku70 in the subject, wherein an abnormal subcellular localization of Ku70 indicates a predisposition to cancer.
- 16. The method of claim 15, wherein the abnormal subcellular localization of Ku70 comprises increased cytosolic localization of Ku70.
- 17. The method of claim 15, wherein the abnormal subcellular localization of Ku70 comprises decreased nuclear localization of Ku70.
- 18. A method of assessing the severity of cancer in a subject comprising:
a. obtaining a nucleic acid sample from the subject; and b. determining whether one or more of the subject's Ku70 alleles or regulatory regions to those alleles are deleted or different from the wild type so as to reduce or eliminate the subject's expression of polypeptide having tumor suppressor activity.
- 19. The method of claim 18, wherein the cancer is T-cell lymphoma.
- 20. The method of claim 18, wherein the cancer is B-cell lymphoma.
- 21. The method of claim 18, wherein the cancer is neuroblastoma.
- 22. A method of assessing the severity of cancer in a subject comprising: determining the subcellular localization of Ku70 in the subject, wherein an abnormal subcellular localization of Ku70 indicates a predisposition to cancer.
- 23. The method of claim 22, wherein the abnormal subcellular localization of Ku70 comprises increased cytosolic localization of Ku70.
- 24. The method of claim 22, wherein the abnormal subcellular localization of Ku70 comprises decreased nuclear localization of Ku70.
- 25. A method of inhibiting the growth of cancer cells, comprising introducing into a cell a Ku70 gene under conditions permitting expression of the gene.
- 26. The method of claim 25, wherein the cancer is T-cell lymphoma.
- 27. The method of claim 25, wherein the cancer is B-cell lymphoma.
- 28. The method of claim 25, wherein the cancer is neuroblastoma.
- 29. The method of claim 25, wherein the cell prior to the introduction of the Ku70 gene was characterized as having a mutation at one or more Ku70 alleles or regulatory regions thereto.
- 30. The method of claim 29, wherein the mutation is a frameshift mutation.
- 31. The method of claim 29, wherein the mutation is a point mutation.
- 32. The method of claim 25, wherein the cell prior to the introduction of the Ku70 gene was characterized as having reduced expression of Ku70.
- 33. The method of claim 25, wherein the Ku70 gene is incorporated into an expression vector prior to introduction into the cell.
- 34. A method of inhibiting the growth of cancer cells, comprising introducing Ku70 into a cell.
- 35. The method of claim 34, wherein the cancer is T-cell lymphoma.
- 36. The method of claim 34, wherein the cancer is B-cell lymphoma.
- 37. The method of claim 34, wherein the cancer is neuroblastoma.
- 38. A transgenic cell, wherein the expression of the Ku70 allele has been altered to increase the susceptibility of the cell to DNA damage.
- 39. A transgenic cell, wherein the expression of the Ku70 allele has been altered to increase the susceptibility of the cell to cancerous growth.
- 40. A transgenic organism, comprising an organism whose germ line cells has been altered at the Ku70 allele to produce an organism whose offspring have an increased likelihood of developing tumors.
- 41. A transgenic organism, comprising an organism whose germ line cells has been altered at the Ku70 allele to produce an organism whose offspring have an increased likelihood of having increased susceptibility to DNA damage.
- 42. The transgenic organism of claim 40, wherein the somatic cells have been altered to reduce or eliminate expression of Ku70.
- 43. The transgenic organism of claim 41, wherein the somatic cells have been alterred to reduce or eliminate expression of Ku70.
- 44. The transgenic organism of claim 40, wherein the organism is a mouse.
- 45. The transgenic organism of claim 41, wherein the organism is a mouse.
- 46. A method of screening a compound for carcinogenic activity, comprising:
a. contacting a cell having reduced expression of Ku70 with the compound; and b. determining whether the compound results in a malignant transformation phenotype.
- 47. The method of claim 46, wherein the cell is a fibroblast.
- 48. The method of claim 46, wherein the malignant transformation phenotype comprises anchorage independent growth.
- 49. A method of screening a compound for DNA damaging activity, comprising:
a. contacting a cell having reduced expression of Ku70 with the compound; and b. determining whether the compound results in DNA damage.
- 50. The method of claim 49, wherein the DNA damage is determined by measuring a reduction in cell survival.
- 51. The method of claim 49, wherein the DNA damage comprises one or more double strand breaks.
- 52. A method of screening a compound for ability to restore Ku70 activity to cells having Ku70 defect symptoms resulting from reduced Ku70 activity, comprising:
a. contacting a cell having reduced expression of Ku70 with the compound; and b. determining whether the compound restores, in whole or in part, a normal Ku70 phenotype.
Parent Case Info
[0001] This application claims the benefit of U.S. provisional Application No. 60/091,188, filed Jun. 30, 1998. The contents of the preceding application are hereby incorporated into this application by reference.
Government Interests
[0002] The invention disclosed herein was made with Government support under NIH Grant Nos. CA-31397 and CA-56909 from the Department of Health and Human Services and the Department of Energy OHER (DC). Accordingly, the U.S. Government has certain rights in this invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60091188 |
Jun 1998 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09343634 |
Jun 1999 |
US |
Child |
10161025 |
Jun 2002 |
US |