Cancer predisposing missense and protein truncating BARD1 mutations in non-BRCA1 or BRCA2 breast cancer families.

TitleCancer predisposing missense and protein truncating BARD1 mutations in non-BRCA1 or BRCA2 breast cancer families.
Publication TypeJournal Article
Year of Publication2010
AuthorsDe Brakeleer, S., J. De Grève, R. Loris, N. Janin, W. Lissens, E. Sermijn, and E. Teugels
JournalHum Mutat
Volume31
Issue3
PaginationE1175-85
Date Published2010 Mar
ISSN1098-1004
KeywordsBreast Neoplasms, Computational Biology, Family Health, Female, Genes, BRCA1, Genes, BRCA2, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Mutation, Mutation, Missense, Ovarian Neoplasms, Pedigree, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases
Abstract

Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported.We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants were analyzed using clinical information as well as IN SILICO predictive tools, including protein modeling. We found three candidate pathogenic mutations in seven families including a first case of a protein truncating mutation (p.Glu652fs) removing the entire second BRCT domain of BARD1. In conclusion, we provide evidence for an increased breast cancer risk associated to specific BARD1 germline mutations. However, these BARD1 mutations occur in a minority of hereditary breast cancer families.

DOI10.1002/humu.21200
Alternate JournalHum. Mutat.
PubMed ID20077502