PARP Inhibitor Insensitivity to <i>BRCA1/2</i> Monoallelic Mutations in Microsatellite Instability-High Cancers

Abstract

MSI-H status and HRD are generally mutually exclusive phenomena across cancer types, but may rarely co-occur, especially in prostate cancer. Although MSI-H samples had a higher <i>BRCAm</i> prevalence relative to microsatellite-stable tumors, these <i>BRCA1/2</i> mutations were generally monoallelic and were not associated with elevated gLOH. Our findings suggest that most <i>BRCAm</i> coexisting with microsatellite instability are likely bystander events that may not result in sensitivity to poly (ADP-ribose) polymerase inhibitors.