title: Cancer predisposing BARD1 mutations in breast-ovarian cancer families.
abstract: The breast cancer susceptibility gene BARD1 (BRCA1-associated RING domain protein, MIM# 601593) acts with BRCA1 in DNA double-strand break (DSB) repair and also in apoptosis initiation. We screened 109 BRCA1/2 negative high-risk breast and/or ovarian cancer patients from North-Eastern Poland for BARD1 germline mutations using a combination of denaturing high-performance liquid chromatography and direct sequencing. We identified 16 different BARD1 sequence variants, five of which are novel. Three of them were suspected to be pathogenic, including a protein truncating nonsense mutation (c.1690C>T, p.Gln564X), a splice mutation (c.1315-2A>G) resulting in exon 5 skipping, and a silent change (c.1977A>G) which alters several exonic splicing enhancer motifs in exon 10 and results in a transcript lacking exons 2-9. Our findings suggest that BARD1 mutations may be regarded as cancer risk alleles and warrant further investigation to determine their actual contribution to non-BRCA1/2 breast and ovarian cancer families.
authors.affiliation: Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland. mratajska@gumed.edu.pl
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ratajska
authors.forename: Ewelina
authors.initials: E
authors.lastname: Antoszewska
authors.forename: Anna
authors.initials: A
authors.lastname: Piskorz
authors.forename: Izabela
authors.initials: I
authors.lastname: Brozek
authors.forename: Åke
authors.initials: Å
authors.lastname: Borg
authors.forename: Hanna
authors.initials: H
authors.lastname: Kusmierek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Janusz
authors.initials: J
authors.lastname: Limon
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases