在有乳腺癌或卵巢癌的车臣患者中，BRCA1 c.3629_3630delAG 致病性变异存在强烈的创始效应。
Strong founder effect for BRCA1 c.3629_3630delAG pathogenic variant in Chechen patients with breast or ovarian cancer.
机构信息
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint-Petersburg, Russia.
Department of Medical Genetics, St.-Petersburg Pediatric Medical University, Saint-Petersburg, Russia.
出版信息
Cancer Med. 2023 Feb;12(3):3167-3171. doi: 10.1002/cam4.5159. Epub 2022 Aug 23.
Coding sequences of BRCA1, BRCA2, ATM, TP53, and PALB2 genes were analyzed in 68 consecutive Chechen patients with high-grade serous ovarian cancer (HGSOC). Pathogenic BRCA1/2 variants were identified in 15 (22%) out of 68 HGSOC cases. Nine out of ten patients with BRCA1 pathogenic alleles carried the same deletion (c.3629_3630delAG), and three out of five BRCA2 heterozygotes had Q3299X allele. The analysis of 49 consecutive patients with triple-negative breast cancer (TNBC) revealed 3 (6%) additional BRCA1 heterozygotes. All women with BRCA1 c.3629_3630delAG allele also carried linked c.1067G>A (Q356R) single nucleotide polymorphism, indicating that this is a genuine founder variant but not a mutational hotspot. An ATM truncating allele was detected in one HGSOC patient. There were no women with TP53 or PALB2 germline alterations. Genetic analysis of non-selected HGSOC patients is an efficient tool for the identification of ethnicity-specific BRCA1/2 pathogenic variants.
对 68 例高级别浆液性卵巢癌（HGSOC）的切里琴患者进行了 BRCA1、BRCA2、ATM、TP53 和 PALB2 基因的编码序列分析。在 68 例 HGSOC 病例中，有 15 例（22%）确定存在致病性 BRCA1/2 变异体。携带 BRCA1 致病性等位基因的 10 名患者中有 9 名携带相同的缺失（c.3629_3630delAG），5 名 BRCA2 杂合子中有 3 名携带 Q3299X 等位基因。对 49 例连续的三阴性乳腺癌（TNBC）患者进行分析，发现另外 3 例（6%）存在 BRCA1 杂合子。所有携带 BRCA1 c.3629_3630delAG 等位基因的女性还携带连锁的 c.1067G>A（Q356R）单核苷酸多态性，这表明这是一个真正的创始人变体，而不是突变热点。在 1 例 HGSOC 患者中检测到 ATM 截断等位基因。没有发现 TP53 或 PALB2 种系改变的女性。对非选择性 HGSOC 患者进行基因分析是确定特定种族的 BRCA1/2 致病性变异体的有效工具。
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