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Familial Cancer
Published in: Familial Cancer 4/2010

01-12-2010

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

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

Published in: Familial Cancer | Issue 4/2010

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Abstract

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.
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Metadata
Title
Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer
Authors
Luca Cavallone
Suzanna L. Arcand
Christine M. Maugard
Serge Nolet
Louis A. Gaboury
Anne-Marie Mes-Masson
Parviz Ghadirian
Diane Provencher
Patricia N. Tonin
Publication date
01-12-2010
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 4/2010
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-010-9372-3

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