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

Abstract

OBJECTIVES:

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

DESIGN:

Observational.

SETTING:

Multisite US-based cohort.

PARTICIPANTS:

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

RESULTS:

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.

CONCLUSIONS:

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.

TRIAL REGISTRATION NUMBER:

NCT01953640; Results.

• Authors: 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
• Journal: BMJ open (BMJ Open) Vol. 6 Issue 4 Pg. e010332 (Apr 15 2016) ISSN: 2044-6055 [Electronic] England
• PMID: 27084275 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chemical References

• BRCA2 Protein
• BRCA2 protein, human
• Neoplasm Proteins

Topics

• Adult
• Aged
• BRCA2 Protein (genetics)
• Exome
• Gene Frequency
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• Male
• Middle Aged
• Neoplasm Proteins (genetics)
• Prostatic Neoplasms, Castration-Resistant (genetics, pathology)