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Breast Cancer Research and Treatment

, Volume 129, Issue 1, pp 255–263 | Cite as

Mutation analysis of RAD51L1 (RAD51B/REC2) in multiple-case, non-BRCA1/2 breast cancer families

  • Julie Johnson
  • Sue Healey
  • Kum Kum Khanna
  • kConFab
  • Georgia Chenevix-Trench
Brief Report

Abstract

Although a significant proportion of familial aggregation of breast cancer remains unexplained, many of the currently known breast cancer susceptibility genes, including BRCA1, BRCA2 and TP53, play a role in maintaining genome integrity by engaging in DNA repair. RAD51L1 is one of the five RAD51 paralogs involved in homologous recombination (HR) repair of DNA double-strand breaks (DSBs); it also interacts directly with p53. Deleterious mutations have been found in one RAD51 paralog, RAD51C (RAD51L2), in non-BRCA1/2 breast and ovarian cancer families, which suggests that all five paralogs are strong candidate breast cancer susceptibility genes. A genome-wide association study (GWAS) has already identified a single nucleotide polymorphism (SNP) deep within intron 10 of RAD51L1 as a risk locus for breast cancer. Based on its biological functions and association with RAD51C, there is reason to suggest that RAD51L1 (RAD51B/REC2) may also contain high risk mutations in the gene that give rise to multiple-case breast cancer families. In order to investigate this hypothesis, we have used high resolution melt (HRM) analysis to screen RAD51L1 for germline mutations in 188 non-BRCA1/2 multiple-case breast cancer families and 190 controls. We identified a total of seven variants: one synonymous, three intronic, and three previously identified SNPs, but no truncating or nonsense changes. Therefore, our results suggest that RAD51L1 is unlikely to represent a high-penetrance breast cancer susceptibility gene.

Keywords

RAD51L1 Familial breast cancer High resolution melt (HRM) analysis Mutation screening 

Notes

Acknowledgments

We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded 2001–2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Julie Johnson was financially supported by a PhD scholarship from the Cancer Council Queensland.

Conflicts of interest

The authors declare that no conflicts of interest exist.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Julie Johnson
    • 1
    • 2
  • Sue Healey
    • 1
  • Kum Kum Khanna
    • 1
  • kConFab
    • 3
  • Georgia Chenevix-Trench
    • 1
  1. 1.Division of Genetics and Population Health, Cancer Genetics LaboratoryQueensland Institute of Medical Research, PO Royal Brisbane HospitalBrisbaneAustralia
  2. 2.School of MedicineUniversity of QueenslandBrisbaneAustralia
  3. 3.Kathleen Cuningham Foundation for Research into Familial Breast Cancer (kConFab)Peter MacCallum Cancer CentreMelbourneAustralia

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