title: Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian breast cancer families.
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.
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Suzanna L
authors.initials: SL
authors.lastname: Arcand
authors.forename: Christine M
authors.initials: CM
authors.lastname: Maugard
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: André
authors.initials: A
authors.lastname: Robidoux
authors.forename: Chantal
authors.initials: C
authors.lastname: Perret
authors.forename: Phil
authors.initials: P
authors.lastname: Zhang
authors.forename: Eve
authors.initials: E
authors.lastname: Fafard
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Diane
authors.initials: D
authors.lastname: Provencher
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
mesh_terms: D000328:Adult; D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D002170:Canada; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D044465:White People
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein