Determining the frequency of pathogenic germline variants from exome sequencing in patients with castrate-resistant prostate cancer.

To determine the frequency of pathogenic inherited mutations in 157 select genes from patients with metastatic castrate-resistant prostate cancer (mCRPC).

Observational.

Multisite US-based cohort.

Seventy-one adult male patients with histological confirmation of prostate cancer, and had progressive disease while on androgen deprivation therapy.

Twelve patients (17.4%) showed evidence of carrying pathogenic or likely pathogenic germline variants in the ATM, ATR, BRCA2, FANCL, MSR1, MUTYH, RB1, TSHR and WRN genes. All but one patient opted in to receive clinically actionable results at the time of study initiation. We also found that pathogenic germline BRCA2 variants appear to be enriched in mCRPC compared to familial prostate cancers.

Pathogenic variants in cancer-susceptibility genes are frequently observed in patients with mCRPC. A substantial proportion of patients with mCRPC or their family members would derive clinical utility from mutation screening.

NCT01953640; Results.

BMJ open. 2016 Apr 15*** epublish ***

Steven N Hart, Marissa S Ellingson, Kim Schahl, Peter T Vedell, Rachel E Carlson, Jason P Sinnwell, Poulami Barman, Hugues Sicotte, Jeanette E Eckel-Passow, Liguo Wang, Krishna R Kalari, Rui Qin, Teresa M Kruisselbrink, Rafael E Jimenez, Alan H Bryce, Winston Tan, Richard Weinshilboum, Liewei Wang, Manish Kohli

Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA., Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA., Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA., Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Division of Hematology/Oncology, Mayo Clinic, Mayo Clinic Cancer Center, Scottsdale, Arizona, USA., Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA., Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, USA.