Synapse - Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination

Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination Journal Article

Authors:	Setton, J.; Selenica, P.; Mukherjee, S.; Shah, R.; Pecorari, I.; McMillan, B.; Pei, I. X.; Kemel, Y.; Ceyhan-Birsoy, O.; Sheehan, M.; Tkachuk, K.; Brown, D. N.; Zhang, L.; Cadoo, K.; Powell, S.; Weigelt, B.; Robson, M.; Riaz, N.; Offit, K.; Reis-Filho, J. S.; Mandelker, D.
Article Title:	Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination
Abstract:	Pathogenic germline mutations in the RAD51 paralog genes RAD51C and RAD51D, are known to confer susceptibility to ovarian and triple-negative breast cancer. Here, we investigated whether germline loss-of-function variants affecting another RAD51 paralog gene, RAD51B, are also associated with breast and ovarian cancer. Among 3422 consecutively accrued breast and ovarian cancer patients consented to tumor/germline sequencing, the observed carrier frequency of loss-of-function germline RAD51B variants was significantly higher than control cases from the gnomAD population database (0.26% vs 0.09%), with an odds ratio of 2.69 (95% CI: 1.4–5.3). Furthermore, we demonstrate that tumors harboring biallelic RAD51B alteration are deficient in homologous recombination DNA repair deficiency (HRD), as evidenced by analysis of sequencing data and in vitro functional assays. Our findings suggest that RAD51B should be considered as an addition to clinical germline testing panels for breast and ovarian cancer susceptibility. © 2021, The Author(s).
Journal Title:	npj Breast Cancer
Volume:	7
ISSN:	2374-4677
Publisher:	Nature Publishing Group
Date Published:	2021-10-11
Start Page:	135
Language:	English
DOI:	10.1038/s41523-021-00339-0
PROVIDER:	scopus
PMCID:	PMC8505423
PUBMED:	34635660
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85116841278&doi=10.1038%2fs41523-021-00339-0&partnerID=40&md5=77c75dce87900a6039f6a3c6678c3360
Notes:	Article -- Export Date: 2 November 2021 -- Source: Scopus