Recurrent gene fusions in prostate cancer

• US 9,926,602 B2
• Filed: 06/11/2014
• Issued: 03/27/2018
• Est. Priority Date: 09/17/2009
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Chinnaiyan, Arul M., Wang, Xiaosong
• Primary Examiner(s): Salmon, Katherine D
• Application Number:
  US14/302,199
• Publication Number:
  US 20140364331A1
• Time in Patent Office: 1,385 Days
• Field of Search: None
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 2800/7028 Cancer

Abstract

The present invention relates to compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention relates to recurrent gene fusions as diagnostic markers and clinical targets for prostate cancer.

Claims

1. A method for detecting a RAF gene fusion in a biological sample, the method comprising:

a) forming a hybridized structure comprising;

i) a nucleic acid comprising a RAF gene fusion comprising a 5′

component joined at a fusion junction to a 3′

component, said 3′

component comprising a rapidly accelerated fibrosarcoma (RAF) kinase domain and said 5′

component comprising a transcriptional regulatory region from an androgen regulated gene; and

ii) a detectably labeled probe specifically hybridized to said nucleic acid and spanning said fusion junction; and

b) detecting the presence of the RAF gene fusion in the biological sample by detecting said hybridized structure in said biological sample.

2. The method of claim 1 wherein the transcriptional regulatory region comprises a promoter region.

3. The method of claim 1 wherein the transcriptional regulatory region comprises an androgen response element.

4. The method of claim 1 comprising detecting wherein said nucleic acid comprising said RAF gene fusion comprises a chromosomal rearrangement of genomic DNA.

5. The method of claim 1 wherein said nucleic acid comprising said RAF gene fusion is a chimeric mRNA transcript.

6. The method of claim 1, wherein the biological sample is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions, and prostate cells.

7. The method of claim 1 wherein said nucleic acid comprising said RAF gene fusion is an amplification product.

8. The method of claim 1 wherein the biological sample is from a patient having or suspected of having prostate cancer.

9. The method of claim 1 further comprising treating a patient that is the source of the biological sample.

10. A method for detecting a RAF gene fusion in a biological sample, the method comprising:

a) forming a hybridized structure comprising;

i) a nucleic acid comprising a RAF gene fusion comprising a 5′

component and a 3′

component, said 3′

component comprising a rapidly accelerated fibrosarcoma (RAF) kinase domain and said 5′

component comprising a transcriptional regulatory region from an androgen regulated gene; and

ii) a first detectably labeled nucleic acid probe specifically hybridized to said 5′

component and a second detectably labeled nucleic acid probe specifically hybridized to said 3′

component; and

b) detecting the presence of the RAF gene fusion in the biological sample by detecting said hybridized structure in said biological sample.

11. The method of claim 10 wherein the transcriptional regulatory region comprises a promoter region.

12. The method of claim 10 wherein the transcriptional regulatory region comprises an androgen response element.

13. The method of claim 10 wherein said nucleic acid comprising said RAF gene fusion comprises a chromosomal rearrangement of genomic DNA.

14. The method of claim 10 wherein said nucleic acid comprising said RAF gene fusion is a chimeric mRNA transcript.

15. The method of claim 10, wherein the biological sample is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions, and prostate cells.

16. The method of claim 10 wherein said nucleic acid comprising said RAF gene fusion is an amplification product.

17. The method of claim 10 wherein the biological sample is from a patient having or suspected of having prostate cancer.

18. The method of claim 10 further comprising treating a patient that is the source of the biological sample.

19. The method of claim 10 wherein detecting said hybridized structure in said biological sample comprises a fluorescence in situ hybridization method.

20. A method for detecting a RAF gene fusion in a biological sample, the method comprising:

a) forming a hybridized structure comprising;

i) a nucleic acid comprising a gene fusion comprising a 5′

component and a 3′

component, said 3′

component comprising a rapidly accelerated fibrosarcoma (RAF) kinase domain and said 5′

component comprising a transcriptional regulatory region from an androgen regulated gene; and

ii) a first amplification primer specifically hybridized to said 5′

component and a second amplification primer specifically hybridized to said 3′

component;

b) amplifying a portion of the nucleic acid using a nucleic acid amplification reaction to produce an amplification product; and

c) detecting the presence of the RAF gene fusion in the biological sample by detecting the gene fusion amplification product.

21. The method of claim 20 wherein the transcriptional regulatory region comprises a promoter region.

22. The method of claim 20 wherein the transcriptional regulatory region comprises an androgen response element.

23. The method of claim 20, wherein the biological sample is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions, and prostate cells.

24. The method of claim 20 wherein the biological sample is from a patient having or suspected of having prostate cancer.

25. The method of claim 20 further comprising treating a patient that is the source of the biological sample.

26. The method of claim 20 wherein detecting the gene fusion amplification product comprises use of a real-time amplification method, a labeled oligonucleotide probe, or an intercalating dye.