Fusion genes associated with progressive prostate cancer

Patent metadata

Field	Value
Publication number	US-10344338-B2
Application number	US-201815896931-A
Country	US
Kind code	B2
Filing date	Feb 14, 2018
Priority date	Dec 30, 2013
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

The present invention relates to methods and compositions for determining whether a subject having prostate cancer is at greater risk of developing progressive disease, and methods of treating the subjects. It is based, at least in part, on the discovery that approximately 90% of men carrying at least one of the following fusion genes: TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67 and CCNH-C5orf30 experienced prostate cancer recurrence, metastases and/or prostate cancer-specific death after radical prostatectomy (each examples of “progressive prostate cancer”), while these outcomes occurred in only 36% of men not carrying any of these fusion genes. It is also based, at least in part, on the discovery that no patient studied survived five years without recurrence if their primary prostate cancer contained a TRMT11-GRIK2 or MTOR-TP53BP1 fusion gene. It is also based, at least in part, on the discovery that the protein encoded by the MAN2A1-FER fusion gene exhibits kinase activity.

First claim

What is claimed is:

1. A kit comprising means for detecting the presence of one or more fusion genes selected from the group consisting of MAN2A1-FER, LRRC59-FLJ60017, TMEM135-CCDC67, PTEN-NOLC1, CCNH-C5orf30, TRMT11-GRIK2, SLC45A2-AMACR, KDM4B-AC011523.2, MTOR-TP53BP, ZMPSTE24-ZMYM4, CLTC-ETV1, ACPP-SEC13, DOCK7-OLR1, PCMTD1-SNTG11 and a combination thereof,
wherein the means for detecting the presence of the one or more fusion genes is selected from the group consisting of one or more pairs of nucleic acid primers, one or more nucleic acid probes, one or more antibodies that bind to the product of the one or more fusion genes and a combination thereof.

2. The kit of claim 1 , wherein the one or more pairs of nucleic acid primers are for polymerase chain reaction (PCR) analysis of the one or more fusion genes.

3. The kit of claim 1 , wherein the one or more nucleic probes are for fluorescence in situ hybridization (FISH) analysis of the one or more fusion genes.

4. The kit of claim 1 , wherein the one or more antibodies that bind to the product of the one or more fusion genes are for Western Blot analysis of the one or more fusion genes.

5. The kit of claim 1 , wherein the one or more fusion genes is the MAN2A1-FER fusion gene.

6. The kit of claim 1 , wherein the one or more fusion genes is the SLC45A2-AMACR fusion gene.

7. The kit of claim 1 , wherein the one or more fusion genes is the PTEN-NOLC1 fusion gene.

8. The kit of claim 1 , wherein the one or more fusion genes is the TMEM135-CCDC67 fusion gene.

9. The kit of claim 1 , wherein the presence of the one or more fusion genes is affixed to a substrate.

10. The kit of claim 1 , wherein the one or more nucleic probes bind to a junction fragment of the fusion gene.

11. The kit of claim 1 , wherein the one or more nucleic probes comprises two nucleic probes that each bind to a component of the fusion gene.

12. The kit of claim 2 , wherein the one or more fusion genes is the MAN2A1-FER fusion gene.

13. The kit of claim 2 , wherein the one or more fusion genes is the SLC45A2-AMACR fusion gene.

14. The kit of claim 2 , wherein the one or more fusion genes is the PTEN-NOLC1 fusion gene.

15. The kit of claim 2 , wherein the one or more fusion genes is the TMEM135-CCDC67 fusion gene.

16. The kit of claim 3 , wherein the one or more fusion genes is the MAN2A1-FER fusion gene.

17. The kit of claim 3 , wherein the one or more fusion genes is the SLC45A2-AMACR fusion gene.

18. The kit of claim 3 , wherein the one or more fusion genes is the PTEN-NOLC1 fusion gene.

19. The kit of claim 3 , wherein the one or more fusion genes is the TMEM135-CCDC67 fusion gene.

20. The kit of claim 4 , wherein the one or more fusion genes is the MAN2A1-FER fusion gene.

21. The kit of claim 4 , wherein the one or more fusion genes is the SLC45A2-AMACR fusion gene.

22. The kit of claim 4 , wherein the one or more fusion genes is the PTEN-NOLC1 fusion gene.

23. The kit of claim 4 , wherein the one or more fusion genes is the TMEM135-CCDC67 fusion gene.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Luo Jianhua
• Yu Yangping
• Nelson Joel B
• Michalopoulos George Konstantine
• Tseng Chien-Cheng
• Ding Ying

Classifications

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q2600/16

  Primer sets for multiplex assays · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title