非小细胞肺癌EGFR、ALK和ROS1基因联合检测及突变共存分析

Combined detection and coexistent genetic mutation analysis of EGFR,ALK and ROS1 in non-small cell lung cancer

目的研究非小细胞肺癌(non-small cell lung cancer,NSCLC)患者中表皮生长因子受体(epidermal growth factor receptor,EGFR)、间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)和C-ros原癌基因1-受体酪氨酸激酶(C-ros oncogene 1-receptor tyrosine kinase,ROS1)驱动基因异常的情况及临床病理特征。方法分析西安交通大学第一附属医院116例NSCLC的临床病理资料,采用扩增阻滞突变系统检测3种驱动基因改变情况,统计分析其与临床病理特征的关系。结果 116例NSCLC中,EGFR突变率36.2%,Exon19 del和Exon21为最常见的2种突变,EGFR外显子的双重突变率为7.1%。在女性、腺癌患者中EGFR的突变率较高,分别为52.3%、45.2%。ALK融合基因阳性率为6.9%;在年龄小于60岁组中的发生率较高,为13.5%。ROS1融合基因阳性率为4.3%,均发生于腺癌和晚期NSCLC患者。本研究还检出少见的EGFR和ALK突变共存1例、EGFR和ROS1突变共存1例。结论 NSCLC中EGFR突变或ALK融合基因较常见,ROS1融合基因稍少见,突变常发生于女性、较年轻的、腺癌患者中;NSCLC驱动基因异常并非绝对互斥,特别是在年轻患者中可出现EGFR和ALK或ROS1突变共存;治疗初期时的多驱动基因联合检测,对促进NSCLC多种分子靶向药物联合治疗具有重要意义。

Objective To investigate the characteristics of epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK)and C-ros oncogene 1-receptor tyrosine kinase(ROS1)driver genes alterations in patients with non-small cell lung cancer(NSCLC).Methods The clinical and pathological data of 116 cases of NSCLC from the First Affiliated Hospital of Xi--an Jiao Tong University were analyzed.Amplification refractory mutation system was used to detect the alterations of the 3 driver genes.The relationship between alterations and clinicopathological features was analyzed statistically.Results Among 116 NSCLCs,the EGFR mutation rate was 36.2%,Exon19 del and Exon21 were the most common 2 mutations,the double mutation rate was 7.1%.The mutation rates of EGFR in female and adenocarcinoma patients were higher,with 52.3%and 45.2%,respectively.The positive rate of ALK fusion gene was 6.9%;the incidence was higher in the group of younger than 60 years old,at 13.5%.The positive rate of ROS1 fusion gene was 4.3%,all of which occurred in adenocarcinoma and advanced NSCLC patients.Interestingly,1 case of a rare case of EGFR and ALK and 1 case of EGFR and ROS1 mutation coexisted were detected.Conclusions EGFR mutation and ALK fusion gene are more common in NSCLC,ROS1 fusion gene is slightly rare.Mutations often occur in female,younger,and adenocarcinoma patients.NSCLC-driven genetic abnormalities are not absolutely mutually exclusive,especially in young patients with the presence of EGFR and ALK or ROS1 mutations.The combined detection of multiple driver genes at the early stage of treatment is critical to the multiple molecular targeting therapies for NSCLC patients.