Inherited mutations in DNA repair genes in men with metastatic castration-resistant prostate cancer.

5009Background: Inherited mutations in genes that regulate DNA repair processes such as BRCA1 and BRCA2 associate with increased risks of developing lethal prostate cancer (PC), and with response to poly-ADP ribose polymerase (PARP) inhibition and platinum chemotherapy. While the prevalence of such mutations in men with localized PC unselected for family predisposition is insufficient to warrant routine testing, the frequency of germline DNA repair gene (DRG) mutations in men with metastatic prostate cancer (mPC) is not established. Methods: We recruited men with mPC (n = 569) through five IRB-approved studies enrolling across seven institutions designed to ascertain molecular aberrations in mPC. Men were unselected for family history of cancer and were documented to have mPC based on a biopsy of a metastatic site. We isolated germ-line DNA from blood lymphocytes, saliva, or tissue uninvolved with cancer and used multiplex sequencing assays to assess germline mutations in 20 DRGs associated with autosomal...