Breast Cancer Research and Treatment

, Volume 108, Issue 3, pp 399–408

Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian breast cancer families

  • Suzanna L. Arcand
  • Christine M. Maugard
  • Parviz Ghadirian
  • André Robidoux
  • Chantal Perret
  • Phil Zhang
  • Eve Fafard
  • Anne-Marie Mes-Masson
  • William D. Foulkes
  • Diane Provencher
  • Steven A. Narod
  • Patricia N. Tonin
Epidemiology

Abstract

About 40% of French Canadian breast and/or ovarian cancer families harbor germline BRCA1 or BRCA1 mutations where common mutations account for about 84% of all mutations identified in cancer families. Within a series of BRCA1 and BRCA2 mutation-negative families, a germline TP53 13398 G>A (Arg213Gln) mutation was identified, which was selected for mutation analysis in this gene because of a family history consistent with Li–Fraumeni syndrome (LFS). Given the founder effects in this population, the 13398 G>A mutation was screened in series of 52 BRCA1 and BRCA2 mutation-negative cancer families, and a mutation-positive family was identified. However, pedigree inspection and expansion of mutation-positive families with the same mutation revealed that they were closely related to each other. To further characterize the contribution of TP53 in cancer families, mutation analysis was performed in the remaining BRCA1 and BRCA2 mutation-negative cancer families. Thirty sequence variants were identified, the majority of which occur in intronic sequences and are not predicted to affect the functionality of TP53. However, the 14538 G>A (Arg290His) mutation was identified in a family which did not exhibit features consistent with LFS or Li–Fraumeni-like (LFL) syndrome. Neither of the TP53 mutations was detected in 381 French Canadian women with breast cancer diagnosed before 50 years of age not selected for family history of cancer. In all, germline TP53 mutations were identified in two of 52 (3.8%) cancer families, suggesting that TP53 is not a major contributor to BRCA1 and BRCA2 mutation-negative breast and/or ovarian cancer families of French Canadian descent.

Keywords

TP53 BRCA1 BRCA2 Breast cancer French Canadian Founder effects 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Suzanna L. Arcand
    • 1
  • Christine M. Maugard
    • 2
    • 3
  • Parviz Ghadirian
    • 4
  • André Robidoux
    • 5
  • Chantal Perret
    • 6
  • Phil Zhang
    • 7
  • Eve Fafard
    • 4
  • Anne-Marie Mes-Masson
    • 3
    • 6
  • William D. Foulkes
    • 1
    • 8
    • 9
    • 10
  • Diane Provencher
    • 6
    • 11
  • Steven A. Narod
    • 7
  • Patricia N. Tonin
    • 1
    • 8
    • 10
    • 12
  1. 1.The Research Institute of the McGill University Health CentreMontrealCanada
  2. 2.Service de Médecine GéniqueCentre Hospitalier de l’Université de Montréal (CHUM)MontrealCanada
  3. 3.Département de médecineUniversité de MontréalMontrealCanada
  4. 4.Epidemiology Research Unit, Research CentreCHUM—Hôtel-DieuMontrealCanada
  5. 5.Department of SurgeryCHUM—Hôtel-DieuMontrealCanada
  6. 6.Centre de Recherche du Centre Hospitalier de l’Université de Montréal/Institut du Cancer de MontréalHôpital Notre-DameMontrealCanada
  7. 7.Women’s College Research InstituteWomen’s College Hospital and University of TorontoTorontoCanada
  8. 8.Program in Cancer Genetics, Departments of Oncology and Human GeneticsMcGill UniversityMontrealCanada
  9. 9.Department of Medical GeneticsSir Mortimer B. Davis-Jewish General HospitalMontrealCanada
  10. 10.Departments of Medicine and Human GeneticsMcGill UniversityMontrealCanada
  11. 11.Département d’obstétrique gynécologie, Division de gynécologie oncologiqueUniversité de MontréalMontrealCanada
  12. 12.Medical GeneticsMontreal General HospitalMontrealCanada

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