Data from Detection of Molecular Signatures of Homologous Recombination Deficiency in Prostate Cancer with or without BRCA1/2 Mutations

Abstract

<div>AbstractPurpose:<p>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.</p>Experimental Design:<p>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; <i>n</i> = 311) and whole-exome sequencing (WES) data (<i>n</i> = 498) of both primary and metastatic prostate adenocarcinomas to determine whether prostate cancer cases display clear signs of HRD in somatic tumor biopsies.</p>Results:<p>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.</p>Conclusions:<p>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).</p></div>