Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.

ABSTRACT: To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted re

SUBMITTER: Decker B 

PROVIDER: S-EPMC4863563 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature