We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation.
- Authors
Seong, M.-W.; Cho, S. I.; Noh, D.-Y.; Han, W.; Kim, S.-W.; Park, C.-M.; Park, H.-W.; Kim, S. Y.; Kim, J. Y.; Park, S. S.
- Abstract
The BRCA1 and BRCA2 genes are the strongest susceptibility genes identified for breast cancer worldwide. However, BRCA1/ BRCA2 have been incompletely investigated due to their large size and the genomic rearrangements that occasionally occur within them. Here we performed a comprehensive mutational analysis for BRCA1/ BRCA2 in 206 Korean patients with breast cancer. We analyzed all exons and flanking regions of BRCA1/ BRCA2 by direct sequencing and screened deletions or duplications involving BRCA1/ BRCA2 by multiplex ligation-dependent probe amplification. We reconstructed haplotypes using intragenic single nucleotide polymorphisms (SNPs) to investigate the possibility of a founder effect among recurrent mutations. In our series, 38 patients (18.4%) had one or more BRCA1/ BRCA2 mutations including 10 novel ones. Three additional patients carried novel distinct unclassified variants with potentially harmful effects. No large deletions or duplications involving BRCA1/ BRCA2 were identified in our series. Haplotype analyses and allele separation suggested that the most frequent mutation in Koreans, BRCA2:c.7480C>T, might have originated from a common ancestor. BRCA1/ BRCA2 mutations were more frequent in a group with family history, bilateral cancer or multiple site cancer than in a group without the risk factors described or an unknown risk group. In contrast, mutation frequencies in the early-onset cancer group were not higher than in the unknown risk group. Our results will be helpful to understand the mutation spectrum in BRCA1/ BRCA2 genes and establish a genetic screening strategy. In addition, this study suggests the possibility of the first true founder mutation of BRCA1/BRCA2 identified in the Korean population.
- Subjects
KOREA; BREAST cancer patients; GENETIC mutation; NUCLEOTIDES; EXONS (Genetics)
- Publication
Clinical Genetics, 2009, Vol 76, Issue 2, p152
- ISSN
0009-9163
- Publication type
Article
- DOI
10.1111/j.1399-0004.2009.01202.x