基于二代测序的宫颈癌突变基因分布情况及相关临床特征分析  

Analysis of gene mutation and related clinical characteristics of cervical cancer based on next generation sequencing

作　　者：李彬 何冬玲 姜德文 吕庆 周箫 刘艳洁[1,2] LI Bin;HE Dongling;JIANG Dewen;LYU Qing;ZHOU Xiao;LIU Yanjie(Department of Pathology,Guizhou Medical University,Guizhou Guiyang 550004,China;Department of Pathology,Affiliated Hospital of Guizhou Medical University,Guizhou Guiyang 550004,China.)

机构地区：[1]贵州医科大学病理教研室,贵州贵阳550004 [2]贵州医科大学附属医院病理科,贵州贵阳550004

出　　处：《现代肿瘤医学》2024年第14期2601-2606,共6页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:81960572);贵州省科技厅科技支撑计划资助项目[编号:黔科合支撑(2019)2791];贵州省贵阳市科技计划资助项目[编号:筑科合同(2019)9-1-16]。

摘　　要：目的:探讨宫颈癌(cervical cancer, CC)体系突变基因及与临床病理特征的关系。方法:选取113例CC患者癌和癌旁组织,提取组织样本的基因组DNA,采用二代测序(next generation sequencing, NGS)技术检测基因体系突变情况并对其突变位点进行筛选、分类和分析。结果:113例CC患者组织样本经NGS共检出324个体系突变基因及相应的3 677个突变位点,包括错义突变、无义突变、5'非编码区突变、沉默突变、内含子突变、3'非编码区突变、非移码缺失突变、移码缺失突变、移码插入突变等共计9种变异类型,其中错义突变占所有变异类型的69.73%(2 564/3 677);KEGG通路富集分析显示突变基因在PI3K-Akt、MAPK等信号通路中富集,TOP20基因互作分析显示,绝大部分突变基因具有协同性。3 677个突变位点中发现166个致病性突变位点,其中47个突变位点在COSMIC、ONCOKBTM和HGMD数据库未收录。统计分析显示致病性突变在HPV感染和肿瘤浸润深度中差异具有统计学意义(P<0.05)。结论:初步阐述了CC中体系突变基因的分布情况,前五位基因(TOP5)分别是PIK3CA、NOTCH1、ERBB2、EGFR和FBXW7,绝大部分基因突变共同发生、具有协同性;87例患者检出致病性突变(76.99%),致病性突变相关的53个基因是潜在的促进CC发生发展的重要因素;新发现47个突变位点可能参与CC发生和发展的致病机制,未来可能成为CC需要关注的突变位点。Objective:To investigate the relationship between somatic mutated genes and clinicopathological features of cervical cancer(CC).Methods:The genomic DNA of 113 CC patients were extracted,the somatic mutations were detected by next generation sequencing technology and the mutant sites were screened,classified and analyzed.Results:A total of 324 somatic mutation gene and their corresponding 3677 mutant sites were detected in tissue samples from 113 CC patients.Including missense mutations,nonsense mutations,5'non-coding mutations,silent mutations,intron mutations,3'non-coding mutations,non-frameshift deletion mutations,frameshift deletion mutations,and frameshift insertion mutations,a total of 9 variation types.Among them,missense mutations accounted for 69.73%(2564/3677)of all variants.KEGG pathway enrichment analysis showed that mutant genes were enriched in PI3K-Akt,MAPK and other signaling pathways,and interaction analysis of TOP20 genes showed that most gene mutations were synergistic.Of the 3677 mutation sites,166 pathogenic mutation sites were identified,of which 47 were not included in the COSMIC,ONCOKB TM and HGMD databases.Statistical analysis showed that the pathogenic mutations were significantly different in the depth of HPV infection and tumor invasion(P<0.05).Conclusion:The distribution of mutant genes in CC system was described.The top five genes were PIK3CA,NOTCH1,ERBB2,EGFR and FBXW7.Most of the mutations were co-occurring and synergistic.Pathogenic mutations were detected in 87 patients(76.99%),and 53 genes associated with pathogenic mutations were potentially important factors to promote the development of CC.47 newly discovered mutation sites may participate in the pathogenesis of CC occurrence and development,and may become the mutation sites that need attention in the future.

关 键 词：宫颈癌 二代测序 突变 基因 临床特征 

分 类 号：R737.33[医药卫生—肿瘤]