Journal
CLINICAL CANCER RESEARCH
Volume 26, Issue 11, Pages 2673-2680Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-19-2135
Keywords
-
Categories
Funding
- Research and Technology Innovation Fund [KTIA_NAP_13-2014-0021, NAP2-2017-1.2.1-NKP-0002]
- Breast Cancer Research Foundation [BCRF-17-156]
- NovoNordisk Foundation Interdisciplinary Synergy Program Grant [NNF15OC0016584]
- Det Fri Forskningsrad [7016-00345B]
- Department of Defense through the Prostate Cancer Research Program [W81XWH-18-2-0056]
- Danish Cancer Society [R90-A6213]
- Velux Foundation [00018310]
Ask authors/readers for more resources
Purpose: Prostate cancers with mutations in genes involved in homologous recombination (HR), most commonly BRCA2, respond favorably to PARP inhibition and platinum-based chemotherapy. We investigated whether other prostate tumors that do not harbor deleterious mutations in these particular genes can similarly be deficient in HR, likely rendering those sensitive to HR-directed therapies. Experimental Design: Homologous recombination deficiency (HRD) levels can be estimated using various mutational signatures derived from next-generation sequencing data. We used this approach on whole-genome sequencing (WGS; n = 311) and whole-exome sequencing (WES) data (n = 498) of both primary and metastatic prostate adenocarcinomas to determine whether prostate cancer cases display clear signs of HRD in somatic tumor biopsies. Results: Known BRCA-deficient samples showed all previously described HRD-associated mutational signatures in the WGS data. HRD-associated mutational signatures were also detected in a subset of patients who did not harbor germline or somatic mutations in BRCA1/2 or other HR-related genes. Similar results, albeit with lower sensitivity and accuracy, were also obtained from WES data. Conclusions: These findings may expand the number of cases likely to respond to PARP inhibitor treatment. On the basis of the HR-associated mutational signatures, 5% to 8% of localized prostate cancer cases may be good candidates for PARP-inhibitor treatment (including those with BRCA1/2 mutations).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available