Germline RAD51C mutations in ovarian cancer susceptibility. (23rd July 2012)

• Record Type: Journal Article
• Authors: Coulet, F; Fajac, A; Colas, C; Eyries, M; Dion‐Minière, A; Rouzier, R; Uzan, S; Lefranc, J‐P; Carbonnel, M; Cornelis, F; Cortez, A; Soubrier, F
• Is Part Of: Clinical genetics. Volume 83:Number 4(2013:Apr.)
• Page Start: 332
• Page End: 336
• Publication Date: 2012-07-23
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/j.1399-0004.2012.01917.x
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Several genes might explain <italic>BRCA1/2</italic> negative breast and ovarian family cases. Deleterious mutations in few genes involved in the Fanconi complex are responsible for Fanconi anemia at the homozygous state and breast cancer (BC) susceptibility at the heterozygous state (<italic>BRCA2, PALB2, BRIP1</italic>). <italic>RAD51C</italic> plays an important role in the double‐strand break repair pathway and a biallelic missense mutation in the <italic>RAD51C</italic> gene was found in a Fanconi anemia‐like disorder. Subsequently, six monoallelic pathogenic mutations were identified after screening 480 <italic>BRCA1/2</italic> negative breast and ovarian cancer (BC/OC) pedigrees. Several reports were unsuccessful to replicate these results. To investigate whether germline mutations in <italic>RAD51C</italic> are associated with an increased risk of developing BC/OC, we screened, by Sanger sequencing of the coding sequence, 117 index cases of breast and ovarian families from French or European origin, and negative for <italic>BRCA1/2</italic> mutations. In our study, we found 3 pathogenic mutations among 117 families screened which corresponds to a 2.6% frequency. Our results confirm that <italic>RAD51C</italic> is a susceptibility gene for ovarian and BC and that this gene should be screened for mutations in families with multiple BC/OC.</p> </abstract>