Germline mutation in the RAD51B gene confers predisposition to breast cancer. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles BMC Cancer Year : 2013

Germline mutation in the RAD51B gene confers predisposition to breast cancer.

Virginie Caux-Moncoutier
  • Function : Author
  • PersonId : 907326
Grégoire Davy
  • Function : Author
  • PersonId : 947587
Essam Al Ageeli
  • Function : Author
  • PersonId : 947588
Brigitte Poirot
  • Function : Author
  • PersonId : 947589
Carole Tirapo
  • Function : Author
  • PersonId : 947590
Dorothée Michaux
  • Function : Author
  • PersonId : 947591
Catherine Barbaroux
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  • PersonId : 918595
Catherine Dubois d'Enghien
  • Function : Author
  • PersonId : 947592
André Nicolas
  • Function : Author
  • PersonId : 947593
Laurent Castéra
  • Function : Author
  • PersonId : 947594
Xavier Sastre-Garau
  • Function : Author
  • PersonId : 943084


BACKGROUND: Most currently known breast cancer predisposition genes play a role in DNA repair by homologous recombination. Recent studies conducted on RAD51 paralogs, involved in the same DNA repair pathway, have identified rare germline mutations conferring breast and/or ovarian cancer predisposition in the RAD51C, RAD51D and XRCC2 genes. The present study analysed the five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) to estimate their contribution to breast and ovarian cancer predisposition. METHODS: The study was conducted on 142 unrelated patients with breast and/or ovarian cancer either with early onset or with a breast/ovarian cancer family history. Patients were referred to a French family cancer clinic and had been previously tested negative for a BRCA1/2 mutation. Coding sequences of the five genes were analysed by EMMA (Enhanced Mismatch Mutation Analysis). Detected variants were characterized by Sanger sequencing analysis. RESULTS: Three splicing mutations and two likely deleterious missense variants were identified: RAD51B c.452 + 3A > G, RAD51C c.706-2A > G, RAD51C c.1026 + 5_1026 + 7del, RAD51B c.475C > T/p.Arg159Cys and XRCC3 c.448C > T/p.Arg150Cys. No RAD51D and XRCC2 gene mutations were detected. These mutations and variants were detected in families with both breast and ovarian cancers, except for the RAD51B c.475C > T/p.Arg159Cys variant that occurred in a family with 3 breast cancer cases. CONCLUSIONS: This study identified the first RAD51B mutation in a breast and ovarian cancer family and is the first report of XRCC3 mutation analysis in breast and ovarian cancer. It confirms that RAD51 paralog mutations confer breast and ovarian cancer predisposition and are rare events. In view of the low frequency of RAD51 paralog mutations, international collaboration of family cancer clinics will be required to more accurately estimate their penetrance and establish clinical guidelines in carrier individuals.


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Dates and versions

inserm-00878230 , version 1 (29-10-2013)



Lisa Golmard, Virginie Caux-Moncoutier, Grégoire Davy, Essam Al Ageeli, Brigitte Poirot, et al.. Germline mutation in the RAD51B gene confers predisposition to breast cancer.. BMC Cancer, 2013, 13 (1), pp.484. ⟨10.1186/1471-2407-13-484⟩. ⟨inserm-00878230⟩
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