广西地区食管鳞状细胞癌热点基因突变谱分析  

Analysis of hot spot gene mutation spectrum of esophageal squamous cell carcinoma in Guangxi

作　　者：王守峰[1] 吴俊伟[1] 苏刘福 叶甲舟[1] Wang Shoufeng;Wu Junwei;Su Liufu;Ye Jiazhou(The Tumor Hospital Affiliated to Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西壮族自治区肿瘤医院,南宁530021

出　　处：《广西医科大学学报》2021年第7期1304-1312,共9页Journal of Guangxi Medical University

基　　金：国家自然青年基金资助项目(No.81803007)。

摘　　要：目的:从基因组学水平系统分析食管鳞状细胞癌(ESCC)发生发展有关热点基因突变特征,分析主要突变类型。方法:收集65例广西地区ESCC患者的癌组织,提取基因组DNA,检测638个癌症热点基因突变情况,分析样本DNA突变信息。结果:通过分析基因编码区的变异结果,65例ESCC样本中发现365个基因发生突变,突变率排名前十的基因分别为TP53、CCND1、FGF19、FGF3、FGF4、CDKN2A、KMT2D、NOTCH1、TP63、ZNF750及LRP1B(并列第10)。基因变异主要类别为拷贝数改变(copy number change)和短变体(short variants)。进一步细分,拷贝数改变以基因扩增(gene amplification)为主,短变体突变类型以替换(substitution)为主。STRING分析突变基因主要富集在以NOTCH1/TP63或者NOTCH1/FGF4为核心的通路中。结论:广西地区ESCC热点基因突变中,主要突变基因为TP53。以NOTCH1为核心的通路可能是潜在的药靶。Objective:To systematically analyze the characteristics of hot spot gene mutations related to the occurrence and development of esophageal squamous cell carcinoma(ESCC)by genomic analysis.Methods:Genomic DNA was extracted from 65 ESCC patients in Guangxi province,638 cancer hot spot gene mutations were detected,and mutation information was analyzed.Results:By analyzing gene coding region mutation results in ESCC samples,mutations were enriched in 365 genes.The top ten genes with mutation rates were TP53,CCND1,FGF19,FGF3,FGF4,CDKN2A,KMT2D,NOTCH1,TP63,ZNF750,and LRP1B(equal tenth).The main types of gene variation were copy number change and short variants.Further subdivision showed that gene amplification was the main cause of copy number change,and substitution was the primary type of short mutation.STRING analysis showed that the mutant genes were mainly concentrated in NOTCH1/TP63 or NOTCH1/FGF4.Conclusion:TP53 is the main mutation gene among the ESCC hot spot genes in Guangxi.NOTCH1 pathway may be a potential drug target.

关 键 词：食管癌 突变 TP53 NOTCH1 

分 类 号：R735.1[医药卫生—肿瘤]