Breast Cancer Research and Treatment

, Volume 127, Issue 3, pp 853–859 | Cite as

BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer

  • Michelle W. Wong
  • Cecilia Nordfors
  • David Mossman
  • Gordana Pecenpetelovska
  • Kelly A. Avery-Kiejda
  • Bente Talseth-Palmer
  • Nikola A. Bowden
  • Rodney J. Scott
Brief Report

Abstract

Mutations in the recognized breast cancer susceptibility genes BRCA1, BRCA2, TP53, ATM, and CHEK2 account for approximately 20% of hereditary breast cancer. This raises the possibility that mutations in other biologically relevant genes may be involved in genetic predisposition to breast cancer. In this study, BRIP1, PALB2, and RAD51C were sequenced for mutations as a result of previously being associated with breast cancer risk due to their role in the double-strand break repair pathway and their close association with BRCA1 and BRCA2. Two truncating mutations in PALB2 (Q66X and W1038X), one of which is has not been reported before, were detected in an independent Australian cohort of 70 individuals with breast or ovarian cancer, and have strong family histories of breast or breast/ovarian cancer. In addition, six missense variants predicted to be causative were detected, one in BRIP1 and five in PALB2. No causative variants were identified in RAD51C. This study supports recent observations that although rare, PALB2 mutations are present in a small but substantial proportion of inherited breast cancer cases, and indicates that RAD51C at a population level does not account for a substantial number of familial breast cancer cases.

Keywords

Hereditary breast cancer BRIP1 PALB2 RAD51C Germline mutations 

Abbreviations

AML

Acute myeloid leukemia

FA

Fanconi anemia

MLPA

Multiplex ligation-dependent probe amplification

PCR

Polymerase chain reaction

SNP

Single nucleotide polymorphism

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Michelle W. Wong
    • 1
  • Cecilia Nordfors
    • 2
  • David Mossman
    • 1
  • Gordana Pecenpetelovska
    • 3
  • Kelly A. Avery-Kiejda
    • 1
  • Bente Talseth-Palmer
    • 1
  • Nikola A. Bowden
    • 1
  • Rodney J. Scott
    • 1
    • 3
  1. 1.Discipline of Medical Genetics and Centre for Information-Based Medicine (CIBM)The University of Newcastle, Hunter Medical Research Institute (HMRI), John Hunter HospitalNewcastleAustralia
  2. 2.Department of Molecular Medicine and Surgery, Karolinska InstitutetKarolinska University Hospital, Solna (L1:00)StockholmSweden
  3. 3.Division of Genetics, Hunter Area Pathology Service (HAPS)John Hunter HospitalNewcastleAustralia

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