Germline mutations in patients with multiple colorectal polyps in China
Germline mutations in patients with multiple colorectal polyps in China
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DOI：
10.1111/jgh.13776
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发表时间：
2017-10-01
影响因子：
4.1
通讯作者：
Sheng, Jian-Qiu
中科院分区：
文献类型：
--
作者：
Li, Chen-Guang;Jin, Peng;Sheng, Jian-Qiu
背景和目的：多发性结直肠息肉与遗传性结直肠癌（CRC）综合征相关，该综合征被认为是由包括种系突变在内的多种事件引起的。本研究旨在探讨中国多发性结直肠息肉患者的种系突变特征。方法：纳入2014年1月至2015年12月解放军总医院消化内科收治的>10个结直肠息肉患者。将这些患者分为高危组、中危组和轻危组。收集白细胞样本，并提取 DNA，通过下一代测序对一组先前与 CRC 相关的 19 个基因进行测序。结果：共有 96 名患者参加了该研究。高危组、中危组和轻危组分别有24例（24/33，72.73%）、9例（9/24，37.5%）和3例（3/39，7.7%）患者存在致病性种系突变。根据给出的结果，我们提出了针对多发性息肉患者进行基因测序检测的策略，该筛查策略的敏感性和特异性分别为97%和57%。八名患有 MUTYH 致病性种系突变的患者中，有四名患有 c.A934-2G 单等位基因种系突变，而八名患者中的三名患有 C55T MUTYH 种系突变。还观察到 APC 和 MUTYH 中同时存在致病性种系突变。结论：包含 19 个基因的遗传筛查策略可有效筛查多发性结直肠息肉患者的遗传性 CRC 综合征。中国患者的 MUTYH 种系突变热点可能与白人患者不同。
Background and Aim: Multiple colorectal polyps are relevant in hereditary colorectal cancer (CRC) syndromes, which are thought to be caused by multiple events including germline mutations. This study was aimed to characterize germline mutations in Chinese patients with multiple colorectal polyps.Methods: Patients with >10 colorectal polyps at the Department of Gastroenterology of the PLA Army General Hospital were enrolled from January 2014 to December 2015. These patients were divided into the high-risk, moderate-risk, and mild-risk groups. White blood cell samples were collected, and DNA was extracted to sequence a panel of 19 genes previously associated with CRC by next-generation sequencing.Results: A total of 96 patients were enrolled in the study. Pathogenic germline mutations were found in 24 (24/33, 72.73%), nine (9/24, 37.5%), and three patients (3/39, 7.7%) in the high-risk, moderate-risk, and mild-risk groups, respectively. Based on the results given, we suggested a strategy about gene sequencing test for the patients with multiple polyps, and the sensitivity and specificity of the screening strategy were 97% and 57%, respectively. Four of eight patients with MUTYH pathogenic germline mutations had the c.A934-2G monoallelic germline mutation, whereas three of eight patients had the C55T MUTYH germline mutation. Concurrent pathogenic germline mutations in APC and MUTYH were also observed.Conclusions: A genetic screening strategy comprising 19 genes was effective to screen for hereditary CRC syndromes in patients with multiple colorectal polyps. The MUTYH germline mutation hotspots in Chinese patients may be different from those in Caucasian patients.