Biallelic Inactivation of BRCA2 in Platinum-sensitive Metastatic Castration-resistant Prostate Cancer

Understanding the molecular underpinnings of sensitivity to specific therapies will advance the goal of precision medicine in prostate cancer (PCa). We identified three patients with metastatic castration-resistant PCa (mCRPC) who achieved an exceptional response to platinum chemotherapy (not first-line treatment for PCa), despite disease progression on prior standard therapies. Using targeted next-generation sequencing on the primary and metastatic tumors, we found that all three patients had biallelic inactivation of BRCA2, a tumor suppressor gene critical for homologous DNA repair. Notably, two had germline BRCA2 mutations, including a patient without compelling family history who was diagnosed at age 66 yr. The third patient had somatic BRCA2 homozygous copy loss. Biallelic BRCA2 inactivation in mCRPC warrants further exploration as a predictive biomarker for sensitivity to platinum chemotherapy.

European urology. 2015 Dec 24 [Epub]

Heather H Cheng, Colin C Pritchard, Thomas Boyd, Peter S Nelson, Bruce Montgomery

Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Northstar Lodge Cancer Center, Yakima, WA, USA., Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA. Electronic address: .

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