Familial Cancer

, Volume 9, Issue 4, pp 507–517 | Cite as

Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer

  • Luca Cavallone
  • Suzanna L. Arcand
  • Christine M. Maugard
  • Serge Nolet
  • Louis A. Gaboury
  • Anne-Marie Mes-Masson
  • Parviz Ghadirian
  • Diane Provencher
  • Patricia N. Tonin


Few studies have reported on the comprehensive BRCA1/2 mutation analyses of hereditary breast cancer (HBC) families of French Canadian descent. Here we report the investigation of 82 families with at least 3 cases of breast cancer evaluated for mutations by DNA sequencing and/or multiplex ligation-dependent probe amplification (MLPA) assay. DNA sequencing identified pathogenic mutations in 37 (45.1%) families, of which 70.2% were one of three recurring mutations (BRCA1:R1443X, BRCA2:8765delAG, and BRCA2:E1953X) frequently reported in this founder population; and variants of uncertain clinical significance in 7 (8.5%) families of which two harbored BRCA2:E3002K. MLPA analysis of the 38 DNA sequence-negative families did not reveal any large rearrangements in BRCA1/2. A phenotypic characterization of the cancer families based on pathogenic mutation status revealed that there were significantly fewer very young age at diagnosis breast cancer cases (<36 years) in mutation-negative families (5.9%, 9 of 153) than in BRCA1 (22.8%, 13 of 57; P = 0.0003) or BRCA2 (22.9%, 27 of 118; P < 1× 10E5) mutation-positive families. There were significantly more mutation-positive families (29 of 36, 80.6%) with a very young age of onset of breast cancer case than those that did not (8 of 39, 20.5%) (P < 10E6). The comprehensive mutation analysis of BRCA1/2 suggests that genomic rearrangements are unlikely to account for sequence-negative HBC families and affirms that the presence of a very young age of diagnosis of breast cancer is strongly predictive of mutation carrier status of French Canadian HBC families.


BRCA1 BRCA2 French Canadian Hereditary breast cancer Multiplex ligation-dependent probe amplification Variant of unknown clinical significance 



Breast Information Core


Hereditary breast cancer


Hereditary breast and ovarian cancer


Human Genome Variation Society


Multiplex ligation-dependent amplification probe assay


Variants of unknown clinical significance

Supplementary material

10689_2010_9372_MOESM1_ESM.pdf (12 kb)
Supplementary material 1 (PDF 13 kb)


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Luca Cavallone
    • 1
  • Suzanna L. Arcand
    • 2
  • Christine M. Maugard
    • 3
    • 4
    • 5
  • Serge Nolet
    • 6
    • 7
  • Louis A. Gaboury
    • 6
    • 7
  • Anne-Marie Mes-Masson
    • 4
    • 5
  • Parviz Ghadirian
    • 8
  • Diane Provencher
    • 5
    • 9
  • Patricia N. Tonin
    • 1
    • 2
    • 10
    • 11
  1. 1.Department of Human GeneticsMcGill UniversityMontrealCanada
  2. 2.The Research Institute of the McGill University Health CentreMontrealCanada
  3. 3.Service de médecine géniqueCentre hospitalier de l’Université de MontréalMontrealCanada
  4. 4.Département de médecineUniversité de MontréalMontrealCanada
  5. 5.Hôpital Notre-DameCentre de recherche du centre hospitalier de l’Université de Montréal/Institut du cancer de MontréalMontrealCanada
  6. 6.Département de pathologieCentre hospitalier de l’Université de MontréalMontrealCanada
  7. 7.Département de pathologie et biologie cellulaire, Faculté de médecineUniversité de MontréalMontrealCanada
  8. 8.Epidemiology Research Unit, Research CentreCentre hospitalier de l’Université de MontréalMontrealCanada
  9. 9.Département d’obstétrique gynécologie, Division de gynécologie oncologiqueUniversité de MontréalMontrealCanada
  10. 10.Department of MedicineMcGill UniversityMontrealCanada
  11. 11.Medical GeneticsMontrealCanada

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