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RAD51C germline mutations found in Spanish site-specific breast cancer and breast-ovarian cancer families

  • Epidemiology
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Abstract

BRCA1 and BRCA2 are the most well-known breast and ovarian cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. Recently, RAD51C, a new Fanconi Anemia gene, essential for homologous recombination repair, has been reported to be a rare hereditary breast and ovarian cancer susceptibility gene. Indeed, several pathogenic mutations have been identified in BRCA1/BRCA2-negative hereditary breast and ovarian cancer families. Here, we present the results of the screening of RAD51C mutations in a large series of 516 BRCA1/BRCA2-negative Spanish patients from breast and/or ovarian cancer families, and the evaluation of these results in the context of all RAD51C carriers. RAD51C mutation screening was performed by DNA analysis for all index cases. All the genetic variants identified were analyzed in silico for splicing and protein predictions. cDNA analysis was performed for three selected variants. All previous RAD51C mutation studies on breast and/or ovarian cancer were reviewed. We identified three inactivating RAD51C mutations. Two mutations were found in breast and ovarian cancer families and one mutation in a site-specific breast cancer family. Based on the mean age of ovarian cancer diagnosis in RAD51C carriers, we would recommend prophylactic bilateral salpingo-ophorectomy in premenopausal RAD51C mutation carriers. Our results support that RAD51C is a rare breast and ovarian cancer susceptibility gene and may contribute to a small fraction of families including breast and ovarian cancer cases and families with only breast cancer. Thus, RAD51C testing should be offered to hereditary breast and/or ovarian cancer families without selecting for specific cancer origin.

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Acknowledgments

We are grateful to the families for their cooperation and to the clinical personnel involved in aspects of recruitment and clinical data collection. This study was supported by grants from the Xunta de Galicia (10PXIB 9101297PR) and FMM Foundation given to AV. SGE is funded by a Miguel Servet contract (CP10/00617) from the Spanish Carlos III Health Institute. The research in Barcelona was supported by a Miguel Servet Project Grant CP10/00617 (granted by the I + D+I 2008–2011 and ISCIII-Subdirección General de Evaluación y Fomento de la Investigación) and FIS projects PI12/02585 and PI13/01711 (from the Spanish Instituto de Salud Carlos III research) given to OD and SGE, respectively. We thank Anna Tenés, Miriam Masas and Belinda Rodríguez for technical support.

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Authors and Affiliations

  1. Fundación Pública Galega de Medicina Xenómica-Servicio Galego de Saúde, Grupo de Medicina Xenómica-Universidade de Santiago de Compostela, Spanish Network on Rare Diseases (CIBERER), Instituto de Investigaciones Sanitarias de Santiago, Santiago de Compostela, A Coruña, Spain

    Ana Blanco, Ángel Carracedo & Ana Vega

  2. Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain

    Sara Gutiérrez-Enríquez, Gemma Montalban, Sandra Bonache & Orland Diez

  3. Grupo de Medicina Xenómica-Universidade de Santiago de Compostela, Spanish Network on Rare Diseases (CIBERER), Instituto de Investigaciones Sanitarias de Santiago, Santiago de Compostela, A Coruña, Spain

    Marta Santamariña

  4. Oncogenetics Group, Vall d’Hebron Research Institute (VHIR), Barcelona, Spain

    Sandra Bonache

  5. Oncogenetics Group, Universitat Autonoma de Barcelona, Barcelona, Spain

    Sandra Bonache

  6. Medical Oncology Department, University Hospital of Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain

    Judith Balmaña

  7. University Hospital of Vall d’Hebron, Barcelona, Spain

    Orland Diez

Authors
  1. Ana Blanco
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  2. Sara Gutiérrez-Enríquez
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  9. Ana Vega
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Correspondence to Ana Vega.

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Blanco, A., Gutiérrez-Enríquez, S., Santamariña, M. et al. RAD51C germline mutations found in Spanish site-specific breast cancer and breast-ovarian cancer families. Breast Cancer Res Treat 147, 133–143 (2014). https://doi.org/10.1007/s10549-014-3078-4

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  • DOI: https://doi.org/10.1007/s10549-014-3078-4

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