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A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families

  • Epidemiology
  • Published:
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Abstract

The RAD51C gene has been recently proposed as a high-penetrance breast and ovarian cancer gene. However, early replication studies have failed to confirm the finding. Thus, further studies in larger cohorts should be conducted in order to clarify the role of RAD51C as a cancer susceptibility gene. Here, we describe a high-resolution melting analysis (HRMA)-based method developed for presequence screening of RAD51C sequence variants. We have screened RAD51C sequence variants by HRMA in 492 breast cancer patients with family history of breast and/or ovarian cancer that were previously tested negative for BRCA1/2. All variants were confirmed by direct sequencing. We have detected 12 different RAD51C germ-line sequence variants, including eight transitions, two transversion, and two indels (insA, and delT). All these variants generated melting profiles which differ from wild type homozygous controls. Interestingly, we have identified one clearly pathogenic mutation (c.774delT) in the subset of 101 breast and ovarian cancer families, supporting that RAD51C is a human breast and ovarian cancer susceptibility gene.

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Acknowledgments

We wish to thank the patients and their families for their cooperation. This study was supported by research grants FIS 09/00859 and RTICC 06/0020/0021, Instituto de Salud Carlos III (FEDER), Spanish Ministry of Science and Innovation. The study was also supported by Fundacion Mutua Madrileña research grant FMMA-08.

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Authors and Affiliations

  1. Laboratorio de Oncología Molecular, Planta baja sur. Hospital Clínico San Carlos, c/Martín Lagos s/n, 28040, Madrid, Spain

    Atocha Romero, Alicia Tosar, Eduardo Díaz-Rubio, Trinidad Caldés & Miguel de la Hoya

  2. Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, Spain

    Pedro Pérez-Segura, José Ángel García-Saenz & Eduardo Díaz-Rubio

Authors
  1. Atocha Romero
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  2. Pedro Pérez-Segura
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  3. Alicia Tosar
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  4. José Ángel García-Saenz
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  5. Eduardo Díaz-Rubio
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  6. Trinidad Caldés
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  7. Miguel de la Hoya
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Correspondence to Trinidad Caldés or Miguel de la Hoya.

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Romero, A., Pérez-Segura, P., Tosar, A. et al. A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families. Breast Cancer Res Treat 129, 939–946 (2011). https://doi.org/10.1007/s10549-011-1543-x

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  • DOI: https://doi.org/10.1007/s10549-011-1543-x

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