Department of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, Netherlands.
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
Fam Cancer. 2023 Apr;22(2):151-154. doi: 10.1007/s10689-022-00314-z. Epub 2022 Sep 16.
An inherited single nucleotide variant (SNV) in the 5'UTR of the BRCA1 gene c.-107A > T was identified to be related to BRCA1 promoter hypermethylation and a hereditary breast and ovarian cancer phenotype in two UK families. We investigated whether this BRCA1 variant was also present in a Dutch cohort of breast and ovarian cancer patients with tumor BRCA1 promoter hypermethylation. We selected all breast and ovarian cancer cases that tested positive for tumor BRCA1 promoter hypermethylation at the Netherlands Cancer Institute and Sanger sequenced the specific mutation in the tumor DNA. In total, we identified 193 tumors with BRCA1 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 in BRCA1. We therefore can conclude that the germline SNV is not pervasive in patients with tumor BRCA1 promoter hypermethylation.
在两个英国家庭中，BRCA1 基因 5'UTR 中的一个遗传单核苷酸变异（SNV）c.-107A > T 被确定与 BRCA1 启动子超甲基化和遗传性乳腺癌和卵巢癌表型有关。我们研究了这种 BRCA1 变体是否也存在于荷兰一组肿瘤 BRCA1 启动子超甲基化的乳腺癌和卵巢癌患者中。我们选择了荷兰癌症研究所所有肿瘤 BRCA1 启动子超甲基化检测呈阳性的乳腺癌和卵巢癌病例，并对肿瘤 DNA 中的特定突变进行了 Sanger 测序。总共在 178 个独特的患者中鉴定出 193 个具有 BRCA1 启动子超甲基化的肿瘤。在 193 个测序的肿瘤样本中，均鉴定出野生型等位基因（100%，193/193）。在一个包含 178 名患者的大队列中，没有患者的肿瘤携带先前在 BRCA1 中鉴定出的 c.-107A > T SNV。因此，我们可以得出结论，胚系 SNV 在肿瘤 BRCA1 启动子超甲基化的患者中并不普遍。
