Cancer predisposing BARD1 mutations in breast–ovarian cancer families
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Magdalena Ratajska Ewelina Antoszewska Anna Piskorz Izabela Brozek A ° ke Borg Hanna Kusmierek Wojciech Biernat Janusz Limon
- چاپ و سال / کشور: 2011
Description
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.
DOI 10.1007/s10549-011-1403-8 Received: 16 December 2010 / Accepted: 8 February 2011
