机构：[1]Department of Respiratory Medicine , Center for Molecular Medicine, Xiangya Hospital , Central South University , Changsha , China.[2]Department of Respiratory Medicine, First Affiliated Hospital , Guangzhou Medical University , Guangzhou , China.[3]Guangdong Lung Cancer Institute , Guangzhou , China.广东省人民医院[4]Shanghai Lung Cancer Center, Shanghai Chest Hospital , Shanghai Jiao Tong University , Shanghai , China.[5]Department of Oncology, Shanghai Pulmonary Hospital , Tongji University Medical School , Shanghai , China.[6]Department of Respiratory Medicine , Zhongshan Hospital, Fudan University , Shanghai , China.[7]Zhejiang Cancer Hospital , Hangzhou , China.浙江省肿瘤医院[8]Department of Oncology, West China Hospital , Sichuan University , Chengdu , China.四川大学华西医院[9]First Affiliated Hospital , Nanjing Medical University , Nanjing , China.[10]First Affiliated Hospital , Zhengzhou University , Zhengzhou , China.[11]Burning Rock Biotech , Guangzhou , China.
Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on in cis compound EGFR mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of EGFR in cis compound mutations and the efficacy of EGFR-TKI in this population. Of the 3,000 patients screened, 1,266 (42.2%) had EGFR mutation; among them, 15 patients (1.2%) harboring in cis compound EGFR mutations, with 10 patients carrying EGFR L858R in combination with a rare mutation and five patients carrying two rare EGFR mutations. No patient with EGFR 19del was observed. Interestingly, no in trans configuration was identified in this cohort. All of the patients harboring in cis compound EGFR mutations were non-smokers, histologically diagnosed with adenocarcinoma and received first-generation EGFR-TKI. Furthermore, our data also revealed that patients with in cis compound EGFR mutations exhibit comparable PFS to first generation EGFR-TKI comparing to patients with single activating EGFR mutation. This observation was further supported by in silico molecular modeling analyses which demonstrated in cis compound mutations do not alter the ATP-binding pocket of EGFR, thus having no effect on the interaction between gefitinib and EGFR.
基金：
This investigation was supported by National Key R&D Program of China (2016YFC1303300) and Xiangya clinical big data system construction project of Central South University (Clinical big data construction project of lung cancer).
第一作者机构：[1]Department of Respiratory Medicine , Center for Molecular Medicine, Xiangya Hospital , Central South University , Changsha , China.
通讯作者：
通讯机构：[1]Department of Respiratory Medicine , Center for Molecular Medicine, Xiangya Hospital , Central South University , Changsha , China.[*1]Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
推荐引用方式(GB/T 7714)：
Li Min,Zhou Cheng-Zhi,Yang Jin-Ji,et al.The in cis compound EGFR mutations in Chinese advanced non-small cell lung cancer patients.[J].CANCER BIOLOGY & THERAPY.2019,20(8):1097-1104.doi:10.1080/15384047.2019.1595280.
APA：
Li Min,Zhou Cheng-Zhi,Yang Jin-Ji,Lu Shun,Zheng Di...&Hu Cheng-Ping.(2019).The in cis compound EGFR mutations in Chinese advanced non-small cell lung cancer patients..CANCER BIOLOGY & THERAPY,20,(8)
MLA：
Li Min,et al."The in cis compound EGFR mutations in Chinese advanced non-small cell lung cancer patients.".CANCER BIOLOGY & THERAPY 20..8(2019):1097-1104
