Chang Pi-Yueh, Chang Shih-Cheng, Wang Mei-Chia, Chen Jinn-Shiun, Tsai Wen-Sy, You Jeng-Fu, Chen Chia-Chun, Liu Hsiu-Ling, Chiang Jy-Ming
Department of Laboratory Medicine, Chang Gung Memorial Hospital, No. 5 Fu-Shing St. Kweishan, Taoyuan 33305, Taiwan.
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, No. 259, Wenhua 1st Rd., Kweishan, Taoyuan 33302, Taiwan.
Cancers (Basel). 2020 Nov 28;12(12):3560. doi: 10.3390/cancers12123560.
Given recent increases in the proportion of early-onset colorectal cancer (CRC), researchers are urgently working to establish a multi-gene screening test for both inherited and sporadic cancer-susceptible individuals. However, the incidence and spectrum of germline mutations in young sporadic CRC patients in East Asian countries and, especially, in sporadic polyp carriers and normal individuals are unknown. Peripheral blood samples were collected from 43 colonoscopy-proved normal controls and from 50 polyp patients and 49 CRC patients with no self-reported family history of cancer. All participants were under 50 years old. Next-generation sequencing with a panel of 30 CRC-associated susceptibility genes was employed to detect pathogenic germline mutations. The germline mutation carrier rates were 2.3%, 4.0%, and 12.2% in the normal, polyp, and cancer groups, respectively. A total of seven different mutations in six DNA repair pathway-related genes ( and ) were detected in nine participants. One frameshift mutation in and one frameshift mutation in the gene were found in a normal control and two colorectal polyp patients, respectively. One young sporadic CRC patient carried two heterozygous mutations, one in and one in . Three mutations (MLH1 p.Arg265Cys, MLH1 p.Tyr343Ter and CHEK2 p.Ile158TyrfsTer10) were each found in two independent patients and were considered "founder" mutations. This is the first report to demonstrate high percentage of germline mutations in young sporadic colorectal polyp, CRC, and general populations. A multi-gene screening test is warranted for the proactive identification of cancer-predisposed individuals.
鉴于近期早发性结直肠癌（CRC）的比例有所上升，研究人员正在紧急开展工作，以建立一种针对遗传性和散发性癌症易感个体的多基因筛查测试。然而，东亚国家年轻散发性CRC患者，尤其是散发性息肉携带者和正常个体中胚系突变的发生率和谱尚不清楚。从43名经结肠镜检查证实的正常对照者、50名息肉患者和49名无癌症家族史报告的CRC患者中采集外周血样本。所有参与者年龄均在50岁以下。采用一组30个与CRC相关的易感基因进行下一代测序，以检测致病性胚系突变。正常组、息肉组和癌症组的胚系突变携带者率分别为2.3%、4.0%和12.2%。在9名参与者中检测到6个DNA修复途径相关基因（和）中的7种不同突变。在一名正常对照者和两名大肠息肉患者中分别发现了基因中的一个移码突变和基因中的一个移码突变。一名年轻的散发性CRC患者携带两个杂合突变，一个在基因中，一个在基因中。在两名独立患者中分别发现了三种突变（MLH1 p.Arg265Cys、MLH1 p.Tyr343Ter和CHEK2 p.Ile158TyrfsTer10），并被认为是“始祖”突变。这是第一份证明年轻散发性大肠息肉、CRC和普通人群中胚系突变比例很高的报告。有必要进行多基因筛查测试，以主动识别癌症易感个体。
