Cancer predisposing BARD1 mutations in breast-ovarian cancer families

BARD1 was identified as a protein interacting with BRCA1 - the heterodimer formed by BRCA1 and BARD1 acts in DNA repair, RNA processing, transcription and cell cycle regulation. BARD1 has also BRCA1-independent functions like mediating p53-dependent apoptosis. Additionally, BARD1 mRNA isoforms were found to be highly expressed in most human gynecological cancers.

We report 17 different BARD1 variants, four of which were suspected to be pathogenic, including a novel substitution (c.1361C>T) leading to amino acid change in highly conserved ankirin domain motif, a splice mutation (c.1315-2A/G) resulting in exon 5 skipping and a silent change (c.1977A/G) which alters several ESE motifs in exon 10, and results in a transcript lacking exons 2-9. Finally we identified two unrelated patients carrying truncating nonsense mutation in exon 8 (c.1690C>T).

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.