METHODS AND COMPOSITIONS FOR IDENTIFYING CANCER-RELATED BIOMARKERS

• US 20070092893A1
• Filed: 09/05/2006
• Published: 04/26/2007
• Est. Priority Date: 09/02/2005
• Status: Abandoned Application

• Current Assignee: University of Toledo
• Original Assignee: University of Toledo
• Inventors: Crawford, Erin, Willey, James, Mullins, D'Anna
• Application Number:
  US11/470,192
• Publication Number:
  US 20070092893A1
• Time in Patent Office: Days
• US Class Current: 435/6.12
• CPC Class Codes: C12Q 1/6809 Methods for determination or identification of nucleic acids involving differential detection
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 33/6842 Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present invention relates to methods and compositions for identifying biomarkers that indicate a biological state, in particular transcription factor biomarkers and genes that can be regulated by such transcription factor biomarkers. The invention also relates to identifying polymorphisms in such transcription factors and regulated genes indicative of the biological state. The biomarkers and polymorphisms identified find use in diagnostic and treatment approaches, e.g., some embodiments the invention provide methods and kits for detecting bronchogenic carcinoma and risks thereof.

Claims

1. A method of identifying a cancer-related condition or a lung-related condition in an subject comprising:

obtaining a sample from said subject, said sample comprising a nucleic acid region corresponding to a 5′

regulatory region of CEBPG; and

comparing said nucleic acid region to a nucleic acid sequence consisting of a 5′

regulatory region of CEBPG±

about 100 bases, wherein a nucleotide difference indicates said cancer or said lung-related condition.

2. The method as recited in claim 1 wherein said comparing comprises identifying at least one base in said nucleic acid region.

3. The method as recited in claim 1 wherein said comparing comprises:

contacting said sample with a probe consisting of a 5′

regulatory region of CEBPG±

about 100 bases or a complementary sequence thereof under conditions allowing hybridization; and

detecting said hybridization.

4. The method as recited in claim 1 wherein said cancer-related condition is bronchogenic carcinoma or a risk thereof.

5. The method as recited in claim 1 wherein said cancer-related condition is responsiveness to a chemotherapeutic agent.

6. The method as recited in claim 1 wherein said lung-related condition is COPD or a risk thereof.

7. The method as recited in claim 1 wherein said nucleotide difference is a single nucleotide polymorphism.

8. The method as recited in claim 1 wherein said nucleotide difference involves 2 nucleotide differences.

9. The method as recited in claim 1 wherein said nucleotide difference involves 3 nucleotide differences.

10. The method as recited in claim 1 wherein said nucleotide difference involves about 10 nucleotide differences.

11. The method as recited in claim 1 wherein said nucleotide difference involves about 50 nucleotide differences.

12. The method as recited in claim 1 wherein said nucleotide difference involves about 100 nucleotide differences.

13. The method as recited in claim 1 wherein said method further comprises identifying an additional nucleotide difference in at least one additional nucleic acid region selected from a 3′

un-translated region of CEBPG;

a bZip coding region of CEBPG; and

a CEPBG recognition site of XRCC1, ERCC1, ERCC2, ERCC5, SOD1, SOD1, CAT, GSTZ1, mGST1, GSTP1 and/or GPX1.

32. The method as recited in claim 1 wherein said comparing comprises identifying at least one base in said nucleic acid region.

33. The method as recited in claim 1 wherein said comparing comprises:

contacting said sample with a probe consisting of a bZip region of CEBPG±

about 100 bases or a complementary sequence thereof under conditions allowing hybridization; and

detecting said hybridization.

34. The method as recited in claim 1 wherein said cancer-related condition is bronchogenic carcinoma or a risk thereof.

35. The method as recited in claim 1 wherein said cancer-related condition is responsiveness to a chemotherapeutic agent.

36. The method as recited in claim 1 wherein said lung-related condition is COPD or a risk thereof.

37. The method as recited in claim 1 wherein said nucleotide difference is a single nucleotide polymorphism.

38. The method as recited in claim 1 wherein said nucleotide difference involves 2 nucleotide differences.

39. The method as recited in claim 1 wherein said nucleotide difference involves 3 nucleotide differences.

40. The method as recited in claim 1 wherein said nucleotide difference involves about 10 nucleotide differences.

41. The method as recited in claim 1 wherein said nucleotide difference involves about 50 nucleotide differences.

42. The method as recited in claim 1 wherein said nucleotide difference involves about 100 nucleotide differences.

43. The method as recited in claim 1 wherein said method further comprises identifying an additional nucleotide difference in at least one additional nucleic acid region selected from a 5′

regulatory region of CEBPG;

a 3′

un-translated region of CEBPG; and

a CEPBG recognition site of XRCC1, ERCC1, ERCC2, ERCC5, SOD1, SOD1, CAT, GSTZ1, mGST1, GSTP1 and/or GPX1.

47. The method as recited in claim 1 wherein said comparing comprises identifying at least one base in said nucleic acid region.

48. The method as recited in claim 1 wherein said comparing comprises:

contacting said sample with a probe consisting of a CEBPG recognition site of XRCC1, ERCC1, ERCC2, ERCC5, SOD1, SOD1, CAT, GSTZ1, mGST1, GSTP1 and/or GPX1±

about 100 bases or a complementary sequence thereof under conditions allowing hybridization; and

detecting said hybridization.

49. The method as recited in claim 1 wherein said cancer-related condition is bronchogenic carcinoma or a risk thereof.

50. The method as recited in claim 1 wherein said cancer-related condition is responsiveness to a chemotherapeutic agent.

51. The method as recited in claim 1 wherein said lung-related condition is COPD or a risk thereof.

52. The method as recited in claim 1 wherein said nucleotide difference is a single nucleotide polymorphism.

53. The method as recited in claim 1 wherein said nucleotide difference involves 2 nucleotide differences.

54. The method as recited in claim 1 wherein said nucleotide difference involves 3 nucleotide differences.

55. The method as recited in claim 1 wherein said nucleotide difference involves about 10 nucleotide differences.

56. The method as recited in claim 1 wherein said nucleotide difference involves about 50 nucleotide differences.

57. The method as recited in claim 1 wherein said nucleotide difference involves about 100 nucleotide differences.

58. The method as recited in claim 1 wherein said method further comprises identifying an additional nucleotide difference in at least one additional nucleic acid region selected from a 5′

regulatory region of CEBPG;

a 3′

un-translated region of CEBPG, and a bZip region of CEBPG.

14. A probe for identifying a polymorphism that indicates BC and/or COPD, comprising a nucleic acid sequence consisting of a 5′

regulatory region of CEBPG±

about 100 bases.

15. The probe as recited in claim 14 wherein said probe is anchored to a support.

16. A method of identifying a cancer-related condition or a lung-related condition in an subject comprising:

obtaining a sample from said subject, said sample comprising a nucleic acid region corresponding to a 3′

un-translated region of CEBPG; and

comparing said nucleic acid region to a nucleic acid sequence consisting of a 3′

un-translated region of CEBPG±

about 100 bases, wherein a nucleotide difference indicates said cancer or said lung-related condition.

17. The method as recited in claim 16 wherein said comparing comprises identifying at least one base in said nucleic acid region.

18. The method as recited in claim 16 wherein said comparing comprises:

contacting said sample with a probe consisting of a 3′

un-translated region of CEBPG±

about 100 bases or a complementary sequence thereof under conditions allowing hybridization; and

detecting said hybridization.

19. The method as recited in claim 16 wherein said cancer-related condition is bronchogenic carcinoma or a risk thereof.

20. The method as recited in claim 16 wherein said cancer-related condition is responsiveness to a chemotherapeutic agent.

21. The method as recited in claim 16 wherein said lung-related condition is COPD or a risk thereof.

22. The method as recited in claim 16 wherein said nucleotide difference is a single nucleotide polymorphism.

23. The method as recited in claim 16 wherein said nucleotide difference involves 2 nucleotide differences.

24. The method as recited in claim 16 wherein said nucleotide difference involves 3 nucleotide differences.

25. The method as recited in claim 16 wherein said nucleotide difference involves about 10 nucleotide differences.

26. The method as recited in claim 16 wherein said nucleotide difference involves about 50 nucleotide differences.

27. The method as recited in claim 16 wherein said nucleotide difference involves about 100 nucleotide differences.

28. The method as recited in claim 16 wherein said method further comprises identifying an additional nucleotide difference in at least one additional nucleic acid region selected from a 5′

regulatory region of CEBPG;

a bZip coding region of CEBPG; and

a CEPBG recognition site of XRCC1, ERCC1, ERCC2, ERCC5, SOD1, SOD1, CAT, GSTZ1, mGST1, GSTP1 and/or GPX1.

29. A probe for identifying a polymorphism that indicates BC and/or COPD, comprising a nucleic acid sequence consisting of a 3′

untranslated region of CEBPG±

about 100 bases.

30. The probe as recited in claim 29 wherein said probe is anchored to a support.

31. A method of identifying a cancer-related condition or a lung-related condition in an subject comprising:

obtaining a sample from said subject, said sample comprising a nucleic acid region corresponding to a bZip region of CEBPG; and

comparing said nucleic acid region to a nucleic acid sequence consisting of a bZip region of CEBPG±

about 100 bases, wherein a nucleotide difference indicates said cancer or said lung-related condition.

44. A probe for identifying a polymorphism that indicates BC and/or COPD, comprising a nucleic acid sequence consisting of a bZip region of CEBPG±

about 100 bases.

45. The probe as recited in claim 44 wherein said probe is anchored to a support.

46. A method of identifying a cancer-related condition or a lung-related condition in an subject comprising:

obtaining a sample from said subject, said sample comprising a nucleic acid region corresponding to a CEBPG recognition site of XRCC1, ERCC1, ERCC2, ERCC5, SOD1, SOD1, CAT, GSTZ1, mGST1, GSTP1 and/or GPX1; and

comparing said nucleic acid region to a nucleic acid sequence consisting of a CEBPG recognition site of XRCC1, ERCC1, ERCC2, ERCC5, SOD1, SOD1, CAT, GSTZ1, mGST1, GSTP1 and/or GPX1±

about 100 bases, wherein a nucleotide difference indicates said cancer or said lung-related condition.

59. A probe or identifying a polymorphism that indicates BC and/or COPD, comprising a nucleic acid sequence consisting of a CEBPG recognition site ±

about 100 bases.

60. The probe as recited in claim 59 wherein said probe is anchored to a support.