非小细胞肺癌中c-Met、EGFR、K-Ras和EML4-ALK基因的检测分析  

The analysis of c-Met,EGFR,K-Ras,and EML4-ALK in non-small cell lung cancer

作　　者：王杰[1] 衣素琴 王欢[1] 周珺[1] 国风[1] 

机构地区：[1]苏州大学附属第一医院中心实验室,江苏苏州215006

出　　处：《临床肿瘤学杂志》2015年第10期902-908,共7页Chinese Clinical Oncology

摘　　要：目的探讨非小细胞肺癌(NSCLC)中肝细胞生长因子受体(c-Met)基因扩增与临床病理特征的关系以及分析c-Met与EGFR、K-Ras和EML4-ALK驱动基因的相关性。方法采用荧光原位杂交技术(FISH)检测108例NSCLC患者的c-Met基因扩增情况,实时荧光定量PCR(qRT-PCR)检测EML4-ALK融合基因及c-Met基因表达量,聚合酶链扩增反应(PCR)及直接测序法检测EGFR和K-Ras基因突变情况,并分析c-Met基因与临床病理特征的关系及其与EGFR、K-Ras和EML4-ALK驱动基因的关系。结果 NSCLC中c-Met基因扩增率为1.85%,其在吸烟和非吸烟患者中扩增率分别为2.94%和1.35%;腺癌c-Met基因扩增率为1.23%,鳞癌未发现c-Met基因扩增;仅Ⅰ期和Ⅲ期中分别有1例c-Met基因扩增。NSCLC中EGFR、K-Ras基因突变及EML4-ALK融合基因的阳性率分别为42.59%、5.56%和12.04%。结论 FISH法对c-Met基因扩增检出率与qRT-PCR检测的c-Met基因表达水平基本一致;c-Met基因扩增与EGFR、K-Ras突变及EML4-ALK融合基因之间几乎是不共存的,c-Met扩增与NSCLC患者年龄、性别、吸烟状态、肿瘤组织类型及临床分期无关。Objective To explore the association of the gene amplification of c-Met with the clinical and pathological features in non-small cell lung cancer（ NSCLC） patients,and the correlation with other driver genes such as EGFR,K-Ras and EML4-ALK.Methods The c-Met gene amplification status was detected by fluorescence in situ hybridization（ FISH） in the 108 cases of NSCLC specimens. The expression of c-Met and EML4-ALK fusion gene were detected by real-time quantitative PCR（ qRT-PCR）. Mutations of EGFR and K-Ras were detected using PCR-based direct sequencing. The correlation of the gene amplification of c-Met with clinicopathologic features and the other driver genes such as EGFR,K-Ras,and EML4-ALK was analyzed. Results（ 1） Among 108 NSCLC patients,c-Met gene amplification was observed in two cases（ 1. 85%）. The proportions of c-Met gene amplification in smokers and non-smokers were 2. 94% and 1. 35%,respectively. The c-Met gene amplification was detected in 1. 23% adenocarcinoma patients but none in squamous carcinoma patients. There was separately one patient harboring c-Met gene amplification in stageⅠand stage Ⅲ（ 2. 50%;5. 00%）.（ 2） The mutation rates of the EGFR and K-Ras gene were 42. 59% and 5. 56%. The positive rate of EML4-ALK fusion gene was12. 04%. Conclusion The proportion of the gene amplification of c-Met detected by FISH was consistent with c-Met expression levels analysed by qRT-PCR. The four driver genes were almost mutually exclusive. And no correlation was found between c-Met gene amplification and various clinicopathologic features such as age,sex,smoking status,histological types,and clinical stages.

关 键 词：非小细胞肺癌 C-MET EGFR K-RAS EML4-ALK 

分 类 号：R734.2[医药卫生—肿瘤]