Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination.
Journal
NPJ breast cancer
ISSN: 2374-4677
Titre abrégé: NPJ Breast Cancer
Pays: United States
ID NLM: 101674891
Informations de publication
Date de publication:
11 Oct 2021
11 Oct 2021
Historique:
received:
17
07
2020
accepted:
24
08
2021
entrez:
12
10
2021
pubmed:
13
10
2021
medline:
13
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34635660
doi: 10.1038/s41523-021-00339-0
pii: 10.1038/s41523-021-00339-0
pmc: PMC8505423
doi:
Types de publication
Journal Article
Langues
eng
Pagination
135Subventions
Organisme : NCI NIH HHS
ID : K12 CA184746
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2021. The Author(s).
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