Breast Cancer Research and Treatment

, Volume 131, Issue 1, pp 333–340 | Cite as

The BRCA2 c.9004G>A (E2003K) variant is likely pathogenic and recurs in breast and/or ovarian cancer families of French Canadian descent

  • Stephanie Cote
  • Suzanna L. Arcand
  • Robert Royer
  • Serge Nolet
  • Anne-Marie Mes-Masson
  • Parviz Ghadirian
  • William D. Foulkes
  • Marc Tischkowitz
  • Steven A. Narod
  • Diane Provencher
  • Patricia N. Tonin
Brief Report

Abstract

Specific BRCA1 and BRCA2 mutations recur in French Canadian breast and/or ovarian cancer families because of common ancestors, facilitating carrier detection in this population. We recently reported a BRCA2 c.9004G>A variant of unknown clinical significance in two French Canadian breast cancer families. It confers a E3002K alteration in the conserved C-terminus domain of BRCA2, and has been reported in non-French Canadian cancer families. Seven variant positive French Canadian families have since been identified by mutation screening of referrals to hereditary cancer clinics. In this article, we describe the cancer phenotypes of these families and further assess the contribution of this variant in the French Canadian population. We screened index breast cancer cases from 58 cancer families with at least three confirmed cases of breast and/or ovarian cancer and 960 breast cancer cases (48 years mean age) not selected for family history of cancer that were previously found not to carry the most common BRCA1 and BRCA2 mutations reported in this population. The index variant-positive cases from each family had breast cancer between the ages of 35–55 years (43 years mean age); and reported close relatives with breast cancer diagnoses between the ages of 28–84 years (57 years mean age). Three families had ovarian or peritoneal cancers. BRCA2-associated cancers, such as bladder, esophagus, pancreas, prostate, and thyroid cancers also occurred in these families. One c.9004G>A carrier also harbored the PALB2 c.2323C>T (Q775X) mutation found to recur in French Canadian breast cancer cases. No new BRCA2 variant carriers were identified in mutation screens. The absence of BRCA2 c.9004G>A carriers in the breast cancer cases not selected for family history contrasts with familial cases, supporting a pathogenic status for this variant and addition to the existing common BRCA1 and BRCA2 mutation-screening panel for French Canadian breast and/or ovarian cancer families.

Keywords

BRCA2 E3002K Hereditary breast cancer Variants of unknown clinical significance Founder mutations French Canadians PALB2 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Stephanie Cote
    • 1
    • 2
  • Suzanna L. Arcand
    • 3
  • Robert Royer
    • 4
  • Serge Nolet
    • 5
    • 6
  • Anne-Marie Mes-Masson
    • 7
    • 8
  • Parviz Ghadirian
    • 9
  • William D. Foulkes
    • 3
    • 10
    • 11
    • 12
    • 13
  • Marc Tischkowitz
    • 10
    • 11
  • Steven A. Narod
    • 4
  • Diane Provencher
    • 7
    • 14
  • Patricia N. Tonin
    • 3
    • 12
    • 13
    • 15
  1. 1.Service de Médecine Génique, Département de MédecineCentre Hospitalier de l’Université de MontréalMontrealCanada
  2. 2.Département des Sciences BiomédicalesUniversité de MontréalMontrealCanada
  3. 3.The Research Institute of the McGill University Health CentreMontrealCanada
  4. 4.Department of Public Health, Women’s College Research InstituteThe University of TorontoTorontoCanada
  5. 5.Département de PathologieCentre Hospitalier de l’Université de MontréalMontrealCanada
  6. 6.Département de Pathologie et Biologie CellulaireUniversité de MontréalMontrealCanada
  7. 7.Institut du cancer de MontréalCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)MontrealCanada
  8. 8.Département de MédecineUniversité de MontréalMontrealCanada
  9. 9.Epidemiology Research UnitCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)MontrealCanada
  10. 10.Program in Cancer Genetics, Departments of Oncology and Human GeneticsMcGill UniversityMontrealCanada
  11. 11.Lady Davis Institute, Segal Cancer CentreJewish General HospitalMontrealCanada
  12. 12.Department of MedicineMcGill UniversityMontrealCanada
  13. 13.Department of Human GeneticsMcGill UniversityMontrealCanada
  14. 14.Division of Gynecologic OncologyUniversité de MontréalMontrealCanada
  15. 15.Medical GeneticsMontrealCanada

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