Objective: To discover frequently mutated new gastric cancer-related genes by exome sequencing technology and to analyze mutated their relationships with different clinicopathological phenotypes of gastric cancer. Methods: Tumor samples of gastric cancers and preoperative peripheral blood samples from 30 patients were collected respectively from January to March, 2016 in the department of general surgery, Chinese PLA General Hospital. Exome sequencing on samples were performed. Using peripheral bloods as control, mutations in tumor samples were discovered by Mutect and Varscan. Frequently mutated gastric cancer-related genes were defined as genes mutated more frequently than TP53. Difference between the mutant and wild-type of certain genes were compared on common clinicopathological phenotypes, such as age, gender, tumor position, differentiation, metastasis lymph nodes, etc. Results: There were 27 frequently mutated genes were founded, most of which showed no relationship with clinicopathological phenotypes of gastric cancer. Cases with mutant and wild-type TAS2R43 showed statistically significant difference in gastric body cancer(55.6% vs 9.5%, P=0.022). Cases with mutant and wild-type ANKRD36C showed statistically significant difference in gastric body cancer (62.5% vs 9.1%, P=0.005). Cases with mutant and wild-type ANKRD36 showed statistically significant difference in proximal gastric cancer (8.33% vs 44.4%, P=0.049). Cases with mutant SYNE1 suffer from less metastatic lymph nodes than those with wild types(2.1±2.4 vs 8.8±9.5, P=0.006). Cases with mutant ADAR are younger than those with wild types(50.7±11.5 year vs 64.0±9.8 year, P=0.006). Conclusion: Mutant TAS2R43, ANKRD36 and ANKRD36C were related to location of gastric cancer. Mutant SYNE1 was related to gastric cancer with less lymph nodes metastasis. Mutant ADAR may lead to gastric cancers in younger groups.
目的： 通过全外显子测序筛查胃癌高频突变基因，探讨这些基因的突变型和野生型在胃癌临床病理表型上的差异。 方法： 随机收集2016年1至3月就诊于解放军总医院普通外科的30例胃癌组织及术前外周血，采用二代基因测序方法，以正常血白细胞为对照，识别肿瘤样本突变的基因。选取突变频率高于TP53的基因为高频突变。对比分析高频突变基因的突变型与野生型在年龄、性别、部位、分化程度、淋巴结转移数等常见临床病理表型上的差异。 结果： 共检出27个胃癌相关高频突变基因，大多数与临床病理表型无关。TAS2R43突变型和野生型在胃体癌中差异有统计学意义(55.6%与9.5%，P＝0.022)，ANKRD36C突变型和野生型在胃体癌中差异有统计学意义(62.5%与9.1%，P＝0.005)，ANKRD36突变型和野生型在近端胃癌中差异也具有统计学意义(8.33%与44.4%，P＝0.049)，SYNE1突变型转移淋巴结数目较野生型少(8.8±9.5与2.1±2.4, P＝0.006)，ADAR突变型发病年龄较低(50.7±11.5)与(64.0±9.8)岁，P＝0.006。 结论： TAS2R43、ANKRD36、ANKRD36C突变与胃癌发生部位相关，SYNE1突变型与少淋巴结转移的胃癌相关，ADAR突变与低龄胃癌相关。.
Keywords: Gastric cancer; Mutation; Phenotype; Whole exome sequencing.