Germline mutational profile of Chinese patients under 70 years old with colorectal cancer.
Germline mutational profile of Chinese patients under 70 years old with colorectal cancer.
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中国70岁以下结直肠癌患者种系突变谱
DOI：
10.1002/cac2.12093
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Jiang TJ;Wang F;Wang YN;Hu JJ;Ding PR;Lin JZ;Pan ZZ;Chen G;Shao JY;Xu RH;Zhao Q;Wang F
遗传易感性占结肠直肠癌（CRC）易感性的近三分之一，其终生患病风险为80% - 100%。然而，关于中国CRC患者中遗传CRC相关基因的种系突变的数据很少。本研究旨在评估中国结直肠癌患者中与癌症易感性相关的基因突变的患病率，中西方患者之间的差异，以及表型-基因型相关性。我们回顾性地收集了526例70岁以下的CRC患者的肿瘤样本，这些患者接受了遗传性CRC基因检测。进行了一系列的生物信息学分析和统计比较。我们发现77例患者（14.6%）携带这12个基因的功能变异。前5个突变基因的突变频率分别为：MutL同源物1 (MLH1) 6.5%、MutS同源物2 (MSH2) 5.1%、MSH6 1.0%、PMS1同源物2 (PMS2) 0.8%、WNT信号通路APC调控因子（APC） 0.8%。我们的数据显示，与西方人群相比，所有错配修复（MMR）基因中MSH6和PMS2基因的突变率要高得多。发现MLH1、MSH2和MSH6的突变是互斥的。MLH1或MSH2突变患者的个人癌症史（MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%）和家族史发生率高于无这些突变的患者（MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%），且病变多发于结肠右侧而非左侧（MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%）。MLH1突变患者的I/II期疾病比例高于无MLH1突变患者（70.6% vs. 50.7%）， APC突变患者的息肉发生率高于野生型APC患者（75.0% vs. 17.4%）。这些结果为结直肠癌患者提供了12个相关基因的遗传易感性的全面图景，并表明对结直肠癌遗传易感性进行全面的多基因面板检测可能是临床实践中有益的分析。
Inherited susceptibility accounts for nearly one‐third of colorectal cancer (CRC) predispositions and has an 80%‐100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC‐related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype‐genotype correlation. We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% for MSH6, 0.8% for PMS1 homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations in MLH1, MSH2, and MSH6 were found to be mutually exclusive. Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients with APC mutations than in those with wild‐type APC (75.0% vs. 17.4%). These results provide a full‐scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi‐gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
39.2
作者：
Ladabaum U;Wang G;Terdiman J;Blanco A;Kuppermann M;Boland CR;Ford J;Elkin E;Phillips KA
通讯作者：
Phillips KA
影响因子：
9.8
作者：
Lammi, L;Arte, S;Nieminen, P
通讯作者：
Nieminen, P
影响因子：
45.3
作者：
Lanza, Giovanni;Gafa, Roberta;Cavazzini, Luigi
通讯作者：
Cavazzini, Luigi
影响因子：
29.4
作者：
Hampel, H;Stephens, JA;de la Chapelle, A
通讯作者：
de la Chapelle, A