Identifying the BRCA1 c.-107A   & gt;  T variant in Dutch patients with a tumor BRCA1 promoter hypermethylation

AbstractAn inherited single nucleotide variant (SNV) in the 5 ′UTR of theBRCA1 gene c.-107A  >  T was identified to be related toBRCA1 promoter hypermethylation and a hereditary breast and ovarian cancer phenotype in two UK families. We investigated whether thisBRCA1 variant was also present in a Dutch cohort of breast and ovarian cancer patients with tumorBRCA1 promoter hypermethylation. We selected all breast and ovarian cancer cases that tested positive for tumorBRCA1 promoter hypermethylation at the Netherlands Cancer Institute and Sanger  sequenced the specific mutation in the tumor DNA. In total, we identified 193 tumors withBRCA1 promoter hypermethylation in 178 unique patients. The wild-type allele was identified in 100% (193/193) of sequenced tumor samples. In a large cohort of 178 patients, none had tumors harboring the previously identified c.-107A  >  T SNV inBRCA1. We therefore can conclude that the germline SNV is not pervasive in patients with tumorBRCA1 promoter hypermethylation.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research