Determining risk of prostate tumor aggressiveness

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.

1 .- 15 . (canceled) 
     
     
         16 . A method for evaluating a biopsy sample to determine a likelihood that a prostate tumor will be aggressive:
 (a) detecting copy numbers at a set of genomic regions or portions thereof in a nucleic acid sample from a prostate tumor obtained from a human patient, 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;   (b) scoring each genomic region or portion thereof as diseased or normal, wherein the scoring is determined based on the copy number in the nucleic acid sample from the prostate tumor compared to a reference normal copy number of non-cancerous tissue; and the genomic region 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 normal copy number, or 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) assigning values to each CAPRA-S clinical factor; and   (d) determining a risk score for tumor aggressiveness by statistical analysis that combines copy number scores generated in (b) and CAPRA-S clinical factor values generated in (c) as continuous and individual variables.   
     
     
         17 . The method of  claim 16 , further comprising treating the patient with a prostate cancer therapy when the risk score exceeds a threshold value for prostate tumor aggressiveness. 
     
     
         18 . The method of  claim 16 , 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, the genomic region or portion thereof at human chromosome 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, the genomic region or portion thereof at 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 at human chromosome 8p21.2 comprises a genomic region or portion thereof at chr8:26555762-26676439, the genomic region 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 at human chromosome 16q23.1 or portion thereof comprises a genomic region or portion thereof at chr16:77158148-77311367. 
     
     
         19 . The method of  claim 16 , wherein detecting the set of copy numbers comprises performing comparative genomic hybridization, genomic sequencing, or a genomic amplification reaction assay. 
     
     
         20 . A computer-implemented method for determining a risk of prostate tumor aggressiveness:
 (a) receiving, at one or more computer system(s), information about a set of copy numbers determined from a tumor sample of a prostate tumor for a set of genomic regions or portions thereof, 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;   (b) performing, with one or more processors associated with the computer system(s), a comparison of the set of copy numbers in the tumor sample to a set of reference copy numbers to score the genomic region or portions thereof as diseased or normal, wherein the genomic region is diseased if there is an increase in copy number at the genomic region or portion thereof 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 tumor sample compared to the reference copy number, and if there is a decrease in copy number at the genomic region or portion thereof 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 tumor sample compared to the reference copy number;   (c) receiving, with one or more processors associated with the computer system(s), values for each CAPRA-S clinical factor; and   (d) generating, with one or more processors associated with the computer system(s), a risk factor score by statistical analysis that combines copy number scores generated in (b) and CAPRA-S clinical factor values generated in (c) as continuous and individual variables.