胃黏膜上皮肠化生病变的基因突变分析  

Analysis of gene mutations in gastric intestinal metaplasia lesions

作　　者：郭水龙[1] 闵力 邵琳琳[1] 徐瑞[1] 李鹏[1] 张澍田[1] GUO Shui-long;MIN Li;SHAO Lin-lin(Department of Gastroenterology,Beijing Friendship Hospital,Capital Medical University,National Clinical Research Center for Digestive Disease,Beijing Key Laboratory for Precancerous Lesion of Digestive Disease,Beijing Digestive Disease Center,Beijing 100050,China.)

机构地区：[1]首都医科大学附属北京友谊医院消化分中心国家消化系统疾病临床医学研究中心消化疾病癌前病变北京市重点实验室北京消化中心,北京100050

出　　处：《临床和实验医学杂志》2021年第11期1121-1124,共4页Journal of Clinical and Experimental Medicine

基　　金：国家自然科学基金项目(编号:81670474);北京市医院管理中心消化内科学科协同发展中心重点课题(编号:XXZ01)。

摘　　要：目的本研究旨在分析胃上皮肠化生病变的特征突变谱,并寻找潜在的癌变风险突变。方法纳入2018至2020年首都医科大学附属北京友谊医院收治的11例胃早癌伴肠化生患者,对其切除的肠化生病变组织进行外显子组测序,分析其整体突变负担、突变类型与类别,通过比较TCGA数据库中胃癌的突变图谱,分析潜在风险突变。结果肠化生组织的突变水平为每Mb碱基大约0.92个突变,在各种恶性肿瘤中位于中间水平,高于乳腺癌、前列腺癌等肿瘤类型,已具有部分肿瘤相关特征;错义突变是胃上皮肠化生最常见的变异类型,占67.8%,SNP突变主要以C>A突变为主,C>T突变次之;高频突变基因的突变频率为20%左右,且与胃早癌及进展期腺型胃癌的高频突变基因存在较大差异;进一步分析发现肠化生阶段积累的突变主要由错配修复缺陷产生,部分与吸烟等高危风险因素有关。结论本研究初步揭示了胃黏膜上皮肠化生病变中基因突变的整体情况,提示肠化生阶段积累的突变具有潜在致癌潜力。Objective To analyze the characteristics of high-risk mutations in gastric mucosal intestinal metaplasia,and identify the mutations associated with potential cancer risks.Methods A total of 11 patients with early gastric cancer and intestinal metaplasia admitted to the Beijing Friendship Hospital,Capital Medical University from 2018 to 2020 were included.Exon sequencing was performed for those metaplasia tissues we collected.The tumor mutation burden,mutation types and categories were analyzed.By comparing to the mutation landscape of gastric cancer tissues recorded in TCGA database,the potential risk mutations were proposed.Results The total mutation rate of metaplasia was about 0.92/Mb,equivalently a moderate level among various malignant tumors,which was higher than that of breast cancer,prostate cancer and etc.Missense mutation was the most common variation type of gastric epithelial intestinal metaplasia,accounting for 67.8%of all mutations;C>A mutation was the main mutation,followed by C>T mutation;The mutation frequency of top mutated gene was about 20%,which is quite different from that of GC.The mutations accumulated in the stage of metaplasia were mainly associated with mismatch repair defects,while some were related to high-risk behaviour factors such as smoking.Conclusion This study preliminarily reveals the overall landscape of gene mutations in high-risk metaplasia lesions,and suggests that the mutations accumulated in the stage of intestinal metaplasia maintained carcinogenic potential.

关 键 词：胃黏膜肠化生 胃癌 基因突变 癌变风险 

分 类 号：R735.2[医药卫生—肿瘤]