摘要
目的:对8种与非小细胞肺癌(non-small cell lung cancer,NSCLC)个性化治疗高度相关的驱动基因进行检测,分析基因变异与临床病理特征的关系。方法:收集天津医科大学肿瘤医院2016年6月至2017年8月212例NSCLC患者样本,对EGFR、KRAS、BRAF、ALK、MET、ERBB2、ROS1、RET 8种基因进行高通量测序。结果:8种基因中EGFR基因变异率高达52.8%,其次为KRAS(8.5%)、ALK(8.0%)、ERBB2(6.1%)、MET(3.8%)、BRAF(1.4%)、RET(0.9%)、ROS1(0.9%),75%样本检出至少1个驱动基因变异,驱动基因变异间呈现强烈互斥。最常见的EGFR突变为19外显子缺失和L858R突变,EGFR T790M突变与前面两个突变位点伴随出现。19外显子缺失患者携带非EGFR T790M突变比例低于L858R突变患者携带非EGFR T790M突变比例(P=0.04)。15.2%EGFR突变伴EGFR扩增,携带EGFR扩增且EGFR突变率>40%患者比例高于无EGFR扩增且EGFR突变率>40%患者(P<0.01)。女性、不吸烟、腺癌患者易发生EGFR特别是EGFR敏感突变(P<0.01)。肺腺癌(P=0.013)、临床分期晚(P=0.048)、淋巴结转移(P=0.027)患者携带EGFR扩增比例高。男性(P=0.009)、左侧肺癌(P=0.048),吸烟患者(P=0.037)KRAS突变发生率较高。携带非KRAS突变、ALK融合的患者更年轻(P=0.005,P=0.031),而携带KRAS突变患者年龄较高(P=0.055)。结论:高通量测序可同时高效检测NSCLC患者中8种与靶向治疗相关驱动基因的变异谱,为临床医生的个体化诊疗提供参考,以多基因为基础的高通量测序为NSCLC诊疗提供更多的可能性。
Objective: To detect eight highly related driver genes in non-small cell lung cancer (NSCLC), and to analyze the relationship between gene variations and clinical-pathological features. Methods: We collected 212 NSCLC samples from Tianjin Medical University Cancer Institute and Hospital, and sequenced eight genes which are EGFR, KRAS, BRAF, ALK, MET, ERBB2, ROS1 and RET. Results: EGFR gene variation rate was as high as 52.8%, followed by KRAS (8.5%), ALK (8.0%), ERBB2 (6.1%), MET (3.8%), BRAF (2.4%), RET (0.9%) and ROS2 (0.9%) in eight detecting genes, at least one driver gene variant was detected in 75% samples, and driver gene variant showed strong mutual exclusion. The most common EGFR mutations were 19 exon deletion and L858R mutation, and the mutation of EGFR T790M was accompanied by the above two mutations. The proportion of non-EGFR T790M mutations in patients with exon 19 deletion was lower than that of L858R mutations (P=0.04). There were 15.2% patients with EGFR mutation accompanied by EGFR amplification, and the"proportion of patients with EGFR mutation frequency greater than 40% with EGFR amplification was higher than that without EGFR amplification (P〈0.02). Women, non-smoking, patients with adenocarcinoma were prone to carry EGFR especially EGFR sensitive mutations (P〈0.02). Patients with lung adenocarcinoma (P=0.013), late clinical stage (P=0.048), and lymph node metastasis (P=0.027) had a higher proportion of EGFR amplification. The incidence of KRAS mutation was higher in men, left lung cancer and smoking patients (P=0.009, P=0.048, P=0.037). Patients with non-KRAS mutations, ALK fusions were younger (P=0.O05, P=0.032), and with KRAS mutations were older (P=0.055). Conclusions: Next-generation sequencing (NG5) can simultaneously detect eight highly related driver genes in NSCLC patients to provide evidence for clinicians. NGS based on detection of multiple genes provides more possi-bilities for individualized diagnosis and treatment of NSCLC.
作者
程亚楠
叶英楠
董莉
韩雷
刘芃芃
张蕊
于津浦
Yanan Cheng;Yingnan Ye;Li Dong;Lei Han;Pengpeng Liu;Rui Zhang;Jinpu Yu Cancer(Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Can- cer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, Chin)
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2018年第11期582-588,共7页
Chinese Journal of Clinical Oncology
基金
国家科技支撑计划课题(编号:2015BAI12B15)
国家自然科学基金课题(编号:81472473和81272360)
天津市科技计划项目(编号:13ZCZCSY20300)资助~~
关键词
高通量测序
非小细胞肺癌
驱动基因
个体化诊疗
next-generation sequencing
non-small cell lung cancer (NSCLC)
driver gene
individualized diagnosis and treatment