Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Hum Mutat. 2019 Jun;40(6):729-733. doi: 10.1002/humu.23736. Epub 2019 Mar 18.
Germline mutations in breast cancer susceptibility gene 1 and 2 have previously been estimated to contribute to 13-18% of all epithelial ovarian cancer (EOC). To characterize the prevalence and effect of BRCA1 and BRCA2 mutations in Middle Eastern EOC patients, BRCA mutation screening was performed in 407 unselected ovarian cancer patients using targeted capture and/or Sanger sequencing. A total of 19 different pathogenic variants (PVs) were identified in 50 (12.3%) women. Nine PVs were recurrent accounting for 80% of cases with PVs (40/50) in the entire cohort. Founder mutation analysis revealed only two mutations (c.4136_4137delCT and c.1140dupG) sharing the same haplotypes thus representing founder mutations in the Middle Eastern population. Identification of the mutation spectrum, prevalence, and founder effect in Middle Eastern population facilitates genetic counseling, risk assessment, and development of a cost-effective screening strategy.
先前估计，乳腺癌易感基因 1 和 2 中的种系突变导致了所有上皮性卵巢癌（EOC）的 13-18%。为了描述中东 EOC 患者中 BRCA1 和 BRCA2 突变的流行率和影响，使用靶向捕获和/或 Sanger 测序对 407 例未经选择的卵巢癌患者进行了 BRCA 突变筛查。在 50 名（12.3%）女性中发现了 19 种不同的致病性变异（PVs）。9 种 PV 是复发性的，占整个队列中具有 PVs（40/50）的 80%。创始人突变分析仅发现了两种具有相同单倍型的突变（c.4136_4137delCT 和 c.1140dupG），因此代表了中东人群中的创始人突变。确定中东人群中的突变谱、流行率和创始人效应有助于遗传咨询、风险评估和制定具有成本效益的筛查策略。
