Nothing to declare.
Germline RAD51C mutations in ovarian cancer susceptibility
Article first published online: 23 JUL 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 83, Issue 4, pages 332–336, April 2013
How to Cite
Germline RAD51C mutations in ovarian cancer susceptibility, , , , , , , , , , , .
This paper is dedicated to the memory of Nathalie Davids who actively participated in this work.
- Issue published online: 12 MAR 2013
- Article first published online: 23 JUL 2012
- Accepted manuscript online: 22 JUN 2012 12:05PM EST
- Manuscript Accepted: 15 JUN 2012
- Manuscript Revised: 25 MAY 2012
- Manuscript Received: 4 APR 2012
- breast cancer susceptibility;
- ovarian cancer susceptibility;
- germline mutation
Several genes might explain BRCA1/2 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 (BRCA2, PALB2, BRIP1). RAD51C plays an important role in the double-strand break repair pathway and a biallelic missense mutation in the RAD51C gene was found in a Fanconi anemia-like disorder. Subsequently, six monoallelic pathogenic mutations were identified after screening 480 BRCA1/2 negative breast and ovarian cancer (BC/OC) pedigrees. Several reports were unsuccessful to replicate these results. To investigate whether germline mutations in RAD51C 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 BRCA1/2 mutations. In our study, we found 3 pathogenic mutations among 117 families screened which corresponds to a 2.6% frequency. Our results confirm that RAD51C is a susceptibility gene for ovarian and BC and that this gene should be screened for mutations in families with multiple BC/OC.