Methods for predicting prostate cancer relapse

Patent metadata

Field	Value
Publication number	US-2018230547-A1
Application number	US-201815890789-A
Country	US
Kind code	A1
Filing date	Feb 7, 2018
Priority date	Aug 7, 2015
Publication date	Aug 16, 2018
Grant date	—

Abstract

The present invention relates to methods for determining whether a subject having prostate cancer is at an increased risk for relapse or rapid relapse. It is based, at least in part, on the results of a comprehensive genome analysis of 273 prostate cancer samples, which indicate that the percentage of large size CNVs predicts prostate cancer relapse. In certain embodiments, a method for determining whether a prostate cancer patient has an increased risk of suffering a relapse or a rapid relapse comprises determining the number and size of CNVs in a sample and determining a large size ratio, where if the large size ratio exceeds a particular threshold, the patient is deemed to be at an increased risk for relapse or rapid relapse.

First claim

What is claimed is:

1 . A method of determining that a prostate cancer patient is at an increased risk for relapse or rapid relapse comprising:
(a) determining the number and size of copy number variations (CNVs) in a sample from the patient; and (b) determining a large size ratio,
where if the large size ratio exceeds a particular threshold, the patient is deemed to be at an increased risk for relapse or rapid relapse.

2 . The method of claim 1 , wherein the sample is a blood sample or a tumor sample.

3 . The method of claim 1 , wherein the large size ratio is calculated by dividing the number of CNVs that are larger in size than a cut-off value by the total number of CNVs.

4 . The method of claim 3 , wherein the cut-off value is about 25 kb or about 30 kb and/or wherein a large size ratio equal to or greater than about 0.28 is indicative that the patient is at an increased risk for relapse.

5 . The method of claim 3 , wherein the cut-off value is about 400 kb or about 500 kb and/or wherein a large size ratio equal to or greater than about 0.02 is indicative that the patient is at an increased risk for rapid relapse.

6 . A method of determining that a prostate cancer patient is at a decreased risk for relapse or rapid relapse comprising:
(a) determining the number and size of copy number variations (CNVs) in a sample from the patient; and (b) determining a large size ratio,
where if the large size ratio is less than a particular threshold, the patient is deemed to be at a decreased risk for relapse or rapid relapse.

7 . The method of claim 6 , wherein the sample is a blood sample or a tumor sample.

8 . The method of claim 6 , wherein the large size ratio is calculated by dividing the number of CNVs that are larger in size than a cut-off value by the total number of CNVs.

9 . The method of claim 8 , wherein the cut-off value is about 25 kb or about 30 kb and/or wherein a large size ratio less than about 0.28 is indicative that the patient is at a decreased risk for relapse.

10 . The method of claim 8 , wherein the cut-off value is about 400 kb or about 500 kb and/or wherein a large size ratio less than about 0.02 is indicative that the patient is at a decreased risk for rapid relapse.

11 . A method for treating a prostate cancer patient comprising determining whether the prostate cancer patient is at increased risk for relapse or rapid relapse, where if the prostate cancer patient is deemed to be at an increased risk for relapse or rapid relapse, then performing a prophylactic and/or treatment regimen.

12 . The method of claim 11 , wherein determining whether the prostate cancer patient is at an increased risk for relapse or rapid relapse comprises determining the number and size of copy number variations (CNVs) in a sample from the patient and determining a large size ratio, where if the large size ratio exceeds a particular threshold, the patient is deemed to be at an increased risk for relapse or rapid relapse.

13 . The method of claim 11 , wherein the prophylactic and/or treatment regimen is selected from the group consisting of cryotherapy, radiation therapy, chemotherapy, hormone therapy, biologic therapy, bisphosphonate therapy, high-intensity focused ultrasound, frequent monitoring, frequent prostate-specific antigen (PSA) checks, radical prostatectomy and combinations thereof.

14 . The method of claim 12 , wherein the large size ratio is calculated by dividing the number of CNVs that are larger in size than a cut-off value by the total number of CNVs.

15 . The method of claim 14 , wherein the cut-off value is about 25 kb or about 30 kb and/or wherein a large size ratio equal to or greater than about 0.28 is indicative that the patient is at an increased risk for relapse.

16 . The method of claim 14 , wherein the cut-off value is about 400 or about 500 kb and/or wherein a large size ratio equal to or greater than about 0.02 is indicative that the patient is at an increased risk for rapid relapse.

17 . A method for treating a prostate cancer patient comprising determining whether the prostate cancer patient is at a decreased risk for relapse or rapid relapse, where if the prostate cancer patient is deemed to be at a decreased risk for relapse or rapid relapse, then performing one or more of high-intensity focused ultrasound, watchful waiting, frequent monitoring, frequent PSA checks and/or a biopsy.

18 . The method of claim 17 , wherein determining whether the prostate cancer patient is at a decreased risk for relapse or rapid relapse comprises determining the number and size of copy number variations (CNVs) in a sample from the patient and determining a large size ratio, where if the large size ratio is less than a particular threshold, the patient is deemed to be at a decreased risk for relapse or rapid relapse.

19 . The method of claim 18 , wherein the large size ratio is calculated by dividing the number of CNVs that are larger in size than a cut-off value by the total number of CNVs.

20 . The method of claim 19 , wherein the cut-off value is about 25 kb or about 30 kb and/or wherein a large size ratio less than about 0.28 is indicative that the patient is at a decreased risk for relapse.

21 . The method of claim 19 , wherein the cut-off value is about 400 or about 500 kb and/or wherein a large size ratio less than about 0.02 is indicative that the patient is at a decreased risk for rapid relapse.

22 . The method of claim 1 , further comprising determining one or more of a Gleason grade of the cancer, nomogram and/or fusion gene status.

23 . The method of claim 22 , wherein the fusion gene is selected from the group consisting of TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67, KDM4B-AC011523.2, CCNH-C5orf30, MAN2A1-FER and combinations thereof.

24 . A kit for determining if a prostate cancer patient is at an increased risk for relapse or rapid relapse comprising a means for analyzing the number and size of copy number variations (CNVs) in one or more genes.

25 . The kit of claim 24 , wherein the means for analyzing the number and size of CNVs comprises an array and/or microarray suitable for detecting the CNVs.

26 . The kit of claim 25 , further comprising a software or internet access to software, in electronically readable form, that determines the number and size of CNVs in the one or more genes represented in the array.

27 . The kit of claim 26 , wherein the software (a) determines whether the CNVs exceed or fall below a size cut-off value and (b) determines a large size ratio.

28 . The kit of claim 27 , wherein the large size ratio is calculated by dividing the number of CNVs that are larger in size than the cut-off value by the total number of CNVs.

29 . The kit of claim 24 , further comprising a means for detecting one or more fusion genes within a sample of the prostate cancer patient.

30 . The kit of claim 29 , wherein the means for detecting the one or more fusion genes comprises one or more packaged fusion gene-specific probes and/or primer sets, arrays/microarrays or antibodies for detecting the one or more fusion genes.

31 . The kit of claim 29 , wherein the one or more fusion genes are selected from the group consisting of TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017,

Assignees

• Univ Pittsburgh Commonwealth Sys Higher Education

Inventors

• Luo Jianhua
• Yu Yanping
• Tseng Chien-Cheng
• Liu Shuchang
• Michalopoulos George
• Nelson Joel

Classifications

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q1/6886 Primary

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

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q1/6837

  using probe arrays or probe chips (C12Q1/6874 takes precedence) · CPC title