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Medline ® Abstract for Reference 74

of 'Overview of hereditary breast and ovarian cancer syndromes'

Cancer predisposing BARD1 mutations in breast-ovarian cancer families.
Ratajska M, Antoszewska E, Piskorz A, Brozek I, BorgÅ, Kusmierek H, Biernat W, Limon J
Breast Cancer Res Treat. 2012 Jan;131(1):89-97. Epub 2011 Feb 23.
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.
Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland. mratajska@gumed.edu.pl