A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Mads Thomassen Inge Søkilde Pedersen Ida Vogel Thomas v. O. Hansen Charlotte Brasch-Andersen Claus L. Brasen Dorthe Cru¨ger Lone Sunde
- چاپ و سال / کشور: 2010
Description
Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845?1G[A (c.7617?1G[A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates with a cancer phenotype in 18 Danish families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer risk families, the mutation was identified as the most common BRCA2 mutation in West Denmark, while it is rare in Central and East Denmark and not identified in South Sweden. Haplotype analysis using dense SNP arrays indicated a common founder of the mutation approximately 1,500 years ago.
Breast Cancer Res Treat (2011) 128:179–185 DOI 10.1007/s10549-010-1272-6 Received: 4 November 2010 / Accepted: 16 November 2010 / Published online: 24 December 2010 Springer Science+Business Media, LLC. 2010
