title: Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation.
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.
authors: Department of Laboratory Medicine, Seoul National University Hospital & Clinical Research Institute, Seoul, Korea.
authors: M-W
authors: MW
authors: Seong
authors: Si
authors: S
authors: Cho
authors: D-Y
authors: DY
authors: Noh
authors: W
authors: W
authors: Han
authors: S-W
authors: SW
authors: Kim
authors: C-M
authors: CM
authors: Park
authors: H-W
authors: HW
authors: Park
authors: S Y
authors: SY
authors: Kim
authors: J Y
authors: JY
authors: Kim
authors: S S
authors: SS
authors: Park
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics*; D024682:BRCA2 Protein / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007723:Korea; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein