Pan-Cancer Analysis of BRCA1 and BRCA2 Genomic Alterations and Their Association With Genomic Instability as Measured by Genome-Wide Loss of Heterozygosity

PURPOSE BRCA1 or BRCA2 loss of function results in homologous recombination deficiency (HRD), which is targetable by poly (ADP-ribose) polymerase (PARP) inhibitors and other DNA-damaging agents. In cancers associated with germline BRCA1/2 alterations ( BRCA1/2-associated cancers: breast, ovarian, pancreatic, prostate), BRCA1/2 alterations result in HRD and are biomarkers for PARP inhibitor use. In other (non– BRCA1/2-associated) cancer types,...