Determining risk of prostate tumor aggressiveness

Inventors: Pamela Paris (San Francisco, CA); Matthew Cooperberg (San Francisco, CA); Peter Carroll (San Francisco, CA)

Assignee: The Regents of the University of California

C12Q1/6886 G16B30/00 G16H50/30 C12Q2600/106 C12Q2600/118 C12Q2600/156 C12Q2600/158

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Quick Facts

Patent No.: US 10,968,485
App. No.: 15/455,905
Granted: Apr 6, 2021
Kind: B2

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Abstract

This disclosure relates to methods, computer products, computer-implemented methods, and systems for predicting the probability or risk of prostate cancer recurrence and tumor aggressiveness in a patient. The method is based, in part, on the patient's risk profile that includes the presence/degree of specific copy number variations and predictive clinical factors. The methods and systems can be used to aid in treatment selection.

Claims (19)

1. A method for evaluating a biopsy sample to determine a likelihood that a prostate tumor will be aggressive:

(a) detecting copy numbers for a set of genomic regions or portions thereof in a nucleic acid sample from a biopsy obtained from a human patient that has a prostate tumor having a Gleason score ≤3+3 and clinical stage ≤T2, wherein the set of genomic regions or portions thereof comprises genomic regions or portions thereof at human chromosomes 3q26.2, 3q26.32, 3q26.3, 5p15.1, 7p22.3, 7q11.22, 7q11.23, 7q22.1, 7q31.31, 9q34.1, 11p15.4, 17q21.33, 17q25.3, 22q13.1, 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14.3 and 16q23.1; and

wherein the genomic region or portion thereof at human chromosome 3q26.2 comprises a genomic region or portion thereof at chr3:168805847-168806351, the genomic region or portion thereof at human chromosome 3q26.32 comprises a genomic region or portion thereof at chr3:177272862-177430308, the genomic region or portion thereof at human chromosome 3q26.3 comprises a genomic region or portion thereof at chr3:178951957-178952231, the genomic region or portion thereof at human chromosome 5p15.1 comprises a genomic region or portion thereof at chr5:17412420-17592769, the genomic region or portion thereof at human chromosome 7p22.3 comprises a genomic region or portion thereof at chr7:1062717-1063110 or chr7:2396631-2396986, the genomic region or portion thereof at human chromosome 7q11.22 comprises a genomic region or portion thereof at chr7:69577003-69759243, the genomic region or portion thereof at human chromosome 7q11.23 comprises a genomic region or portion thereof at chr7:73442517-73483030, the genomic region or portion thereof at human chromosome 7q22.1 comprises a genomic region or portion thereof at chr7:100705095-100899914, the genomic region or portion thereof at human chromosome 7q31.31 comprises a genomic region or portion thereof at chr7:117432355-117432817, the genomic region or portion thereof at human chromosome 9q34.1 comprises a genomic region or portion thereof at chr9:132262446-132370055, the genomic region or portion thereof at human chromosome 11p15.4 comprises a genomic region or portion thereof at chr11:2904813-2907001, 17q21.33 comprises a genomic region or portion thereof at chr17:47454237-47654582, the genomic region or portion thereof at human chromosome 17q25.3 comprises a genomic region or portion thereof at chr17:77702278-77862768, the genomic region or portion thereof at human chromosome 22q13.1 comprises a genomic region or portion thereof at chr22:39620241-39631867, the genomic region or portion thereof at human chromosome 4p13 comprises a genomic region or portion thereof at chr4:44558370-44559188, the genomic region or portion thereof at human chromosome 5q13.1 comprises a genomic region or portion thereof at chr5:67803220-67803609, the genomic region or portion thereof at human chromosome 5q14.3 comprises a genomic region or portion thereof at chr5:85936281-86082787, the genomic region or portion thereof at human chromosome 5q21.1 comprises a genomic region or portion thereof at chr5:102652546-102813426, the genomic region or portion thereof at human chromosome 5q21.2 comprises a genomic region or portion thereof at chr5:103047961-103230737, the genomic region or portion thereof at human chromosome 5q21.3 comprises a genomic region or portion thereof at chr5:108476063-108523316, the genomic region or portion thereof at human chromosome 5q23.1 comprises a genomic region or portion thereof at chr5:116987516-116987850, at the genomic region or portion thereof of human chromosome 6q14.1 comprises a genomic region or portion thereof at chr6:79240539-79417494, the genomic region or portion thereof at human chromosome 6q21 comprises a genomic region or portion thereof at chr6:105514625-105687735, the genomic region or portion thereof at human chromosome 6q21 comprises a genomic region or portion thereof at chr6:112401839-112550863, the genomic region or portion thereof at human chromosome 8p22 comprises a genomic region or portion thereof at chr8:15649576-15649945, the genomic region or portion thereof at human chromosome 8p21.2 comprises a genomic region or portion thereof at chr8:25189716-25280826, the genomic region or portion thereof at human chromosome 8p21.2 comprises a genomic region or portion thereof at chr8:26260492-26362544, the genomic region or portion thereof at human chromosome 8p21.2 comprises a genomic region or portion thereof at chr8:26555762-26676439, the genomic region or portion thereof at human chromosome 8p12 comprises a genomic region or portion thereof at chr8:32412399-32572832, the genomic region or portion thereof at human chromosome 10q23.31 comprises a genomic region or portion thereof at chr10:89991491-90075908, the genomic region or portion thereof at human chromosome 13q14.11 comprises a genomic region or portion thereof at chr13:40129477-40205232, the genomic region or portion thereof at human chromosome 13q14.11 comprises a genomic region or portion thereof at chr13:41044273-41044745, the genomic region or portion thereof at human chromosome 13q14.11 comprises a genomic region or portion thereof at chr13:43679675-43868415, the genomic region or portion thereof at human chromosome 13q14.13 comprises a genomic region or portion thereof at chr13:45857696-45858096, the genomic region or portion thereof at human chromosome 13q14.2 comprises a genomic region or portion thereof at chr13:49015662-49140264, the genomic region or portion thereof at human chromosome 13q14.3 comprises a genomic region or portion thereof at chr13:51245126-51245378 and the genomic region or portion thereof at human chromosome 16q23.1 comprises a genomic region or portion thereof at chr16:77158148-77311367;

(b) scoring each genomic region or portion thereof as diseased or normal to generate a copy number score, wherein the scoring is determined based on the copy number in the nucleic acid sample from the biopsy compared to a normal reference copy number of noncancerous tissue; and the genomic region or portion thereof is scored as diseased if there is an increase in copy number at the genomic region or portion thereof located at human chromosome 3q26.2, 3q26.32, 3q26.3, 5p15.1, 7p22.3, 7q11.22, 7q11.23, 7q22.1, 7q31.31, 9q34.1, 11p15.4, 17q21.33, 17q25.3, or 22q13.1 in the nucleic acid sample from the biopsy compared to the reference copy number, and if there is a decrease in copy number at the genomic region or portion thereof located at human chromosome 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14.3 or 16q23.1 in the nucleic acid sample from the biopsy compared to reference copy number;

(c) predicting an increased risk of aggressiveness of the prostate tumor when at least 20% of the genomic regions are scored as diseased; and

(d) treating a patient that is predicted to have an increased risk of aggressiveness of the prostate tumor in (c) with a therapy to kill, inhibit, or remove prostate cancer cells.

2. The method of claim 1 , wherein the patient has not received a therapy to treat the prostate tumor.

3. The method of claim 1 , where the patient has a PSA level of ≤10 ng/ml.

4. The method of claim 1 , further comprising calculating a clinical score based on at least one clinical factor selected from the group consisting of clinical stage, Gleason score, and PSA level.

5. The method of claim 1 , wherein detecting the set of copy numbers comprises performing comparative genomic hybridization, genomic sequencing, or a genomic amplification reaction assay.

6. A method of treating a human patient that has a prostate tumor having a Gleason score ≤3+3 and clinical stage ≤T2, the method comprising:

(a) determining that the human patient has an increased likelihood of having an aggressive prostate tumor by

obtaining or having obtained a nucleic acid sample from a biopsy of the prostate tumor;

detecting or having detected copy number changes in a set of genomic regions or portions thereof in the nucleic acid sample, wherein the set of genomic regions or portions thereof comprises genomic regions or portions thereof at human chromosomes 3q26.2, 3q26.32, 3q26.3, 5p15.1, 7p22.3, 7q11.22, 7q11.23, 7q22.1, 7q31.31, 9q34.1, 11p15.4, 17q21.33, 17q25.3, 22q13.1, 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14.3 and 16q23.1; and

scoring or having scored each genomic region or portion thereof as diseased or normal to generate a copy number score, wherein the scoring is determined based on the copy number in the nucleic acid sample from the biopsy compared to a normal reference copy number of noncancerous tissue; and the genomic region or portion thereof is scored as diseased if there is an increase in copy number at the genomic region or portion thereof located at human chromosome 3q26.2, 3q26.32, 3q26.3, 5p15.1, 7p22.3, 7q11.22, 7q11.23, 7q22.1, 7q31.31, 9q34.1, 11p15.4, 17q21.33, 17q25.3, or 22q13.1 in the nucleic acid sample from the biopsy compared to the reference copy number, and if there is a decrease in copy number at the genomic region or portion thereof located at human chromosome 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14.3 or 16q23.1 in the nucleic acid sample from the biopsy compared to reference copy number;

(b) identifying that the human patient has at least 20% of the genomic regions in the nucleic acid sample scored as diseased and then administering a therapy to kill, inhibit, or remove prostate cancer cells.

7. The method of claim 6 , where the patient has a PSA level of ≤10 ng/ml.

8. The method of claim 6 , further comprising calculating a clinical score based on at least one clinical factor selected from the group consisting of clinical stage, Gleason score, and PSA level.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2017

From: PARIS, PAMELA; COOPERBERG, MATTHEW; CARROLL, PETER

To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Reel/Frame 043142/0897 →

CONFIRMATORY LICENSE Recorded Jun 26, 2017

From: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

To: US ARMY, SECRETARY OF THE ARMY

Reel/Frame 042986/0314 →

Continuity (3)

Continuation In Part PCTUS2016033753 · May 23, 2016

Provisional Application 62165647 · May 22, 2015

Related Publication 20170183744A1 · Jun 29, 2017