二代测序技术检测肺癌相关基因突变状态临床病理意义  

Clinicopathological significance of next generation sequencing in detecting mutation status of lung cancer related genes

作　　者：王琼[1] 吕亚莉[1] 钟梅[1] 董周寰[1] 朱凤伟[1] 石怀银[1] WANG Qiong;Lü Ya-li;ZHONG Mei;DONG Zhou-huan;ZHU Feng-wei;SHI Huai-yin(Department of Pathology,Chinese People＇s Liberation Army General Hospital,Beijing 100853,P.R.China)

机构地区：[1]中国人民解放军总医院病理科,北京100853

出　　处：《中华肿瘤防治杂志》2018年第13期944-950,共7页Chinese Journal of Cancer Prevention and Treatment

基　　金：解放军总医院医疗大数据研发项目(2016MBD-022)

摘　　要：目的肺癌的靶向治疗前需检测相应驱动基因和耐药基因的突变情况。二代测序技术可以单次高通量检测多个基因状态,辅助临床诊疗。本研究探讨二代测序技术检测肺癌相关基因突变状况,并初步分析其突变的临床病理意义。方法回顾性分析解放军总医院2017-06-01-2017-10-30行手术切除及活检的肿瘤组织>20%的肺癌标本123例。采用Ion Torrent二代测序平台分别检测34个基因共586个突变位点,检测结果对照相应的基因数据库分析。结果123例肺癌样本TP53的突变率是93.50%(115/123),EGFR的突变率是43.09%(53/123),KRAS是13.01%(16/123),STK11是8.13%(10/123),ERBB2、BRAF均为6.50%(8/123),CTNNB1是5.69%(7/123),MET是3.25%(4/123),PTEN、MAP2K1均为2.44%(3/123),SMAD4、PIK3CA和IDH1均为1.63%(2/123)。ALK是4.07%(5/123),RET是3.25%(4/123),ROS1是0.81%(1/123)。≥61岁患者的TP53突变率明显高于<61岁,χ~2=3.992,P=0.046。EGFR基因在年龄<61岁(χ~2=6.534,P=0.011)、不吸烟(χ~2=10.559,P=0.001)的患者中突变率明显升高。女性患者的ERBB2突变率高于男性,χ~2=5.081,P=0.024。BRAF基因突变率在分化程度较低的患者中较高,χ~2=8.261,P=0.016。STK11基因突变在年龄≥61岁(χ~2=4.516,P=0.034)、分化程度较低(χ~2=7.465,P=0.006)的患者中突变率较高。检测到的基因突变主要发生在腺泡为主的组织类型,同时查见多个基因突变共存的病例。52.94%(18/34)的被检测基因有特定的靶向药物,47.06%(16/34)的检测基因有尚处于临床实验阶段的靶向药物。结论采用Ion Torrent二代测序平台可以用于临床观察肺癌基因突变谱的改变,对后期选择针对这些基因的靶向治疗具有广阔的应用前景。OBJECTIVE The mutations of drive genes and resistance genes which relevant to targeted drugs were detected before targeted therapy in lung cancer,multiple gene states were tested with a single high-throughput by secondgeneration sequencing technology,thus could be supporting clinical diagnosis and treatment.This study aimed to investigate mutations of lung cancer related genes by second-generation sequencing technology,and preliminarily discuss the clinicopathological significance.METHODS A retrospective analysis was performed to 123 lung cancer cases with more than20%tumor tissue.Ion Torrent second-generation sequencing platform was used to detect 586 mutation sites of 34 genes respectively.The results were compared with the corresponding gene databases.RESULTS In 123 lung cancer samples,the frequencies of TP53,EGFR,KRAS,STK11,ERBB2,BRAF,CTNNB1,MET,MAP2 K1,PTEN,SMAD4,PIK3 CA,IDH1,ALK,RET,ROS1 mutation were respectively 93.50%（115/123）,43.09%（53/123）,13.01%（16/123）,8.13%（10/123）,6.50%（8/123）,6.50%（8/123）,5.69%（7/123）,3.25%（4/123）,2.44%（3/123）,2.44%（3/123）,1.63%（2/123）,1.63%（2/123）,1.63%（2/123）,4.07%（5/123）,3.25%（4/123）,0.81%（1/123）.The mutation rate of TP53 over the age of 61 was significantly higher than that below 61（χ^2=3.992,P=0.046）.EGFR mutation rate was significantly higher in patients with over 61 years（χ^2=6.534,P=0.011）,and higher in non-smoking patients（χ^2=10.559,P=0.001）.Female patients had a higher ERBB2 mutation rate than male（χ^2=5.081,P=0.024）.BRAF mutation rate was higher in poorly differentiation tumors（χ^2=8.261,P=0.016）.STK11 mutation rate was higher in patients with over61 years（χ^2=4.516,P=0.034）,also higher in patients with poorly-differentiated（χ^2=7.465,P=0.006）.Detected gene mutations were mainly happened in the type of tissue dominated by acinus,at the same time coexistence of gene mutations were found in several cases.Totally 52.94%（18/34）of the tested genes had specific targeted dru

关 键 词：二代测序 肺癌 ALK EGFR 

分 类 号：R734.2[医药卫生—肿瘤]