Identification of MET Exon 14 skipping by targeted RNA-based next-generation sequencing in Chinese Patients with NSCLC.

Abstract

e20018 Background: MET (mesenchymal-epithelial transition) exon14 skipping mutations have been reported to represent a clinically unique molecular subtype of NSCLC. The prevalence rates of MET exon 14 skipping in lung adenocarcinoma are quite different, from 0.9% to 4.0% in Asian populations. Since some somatic variants not covering the MET exon 14 splice sites might also induce MET exon 14 skipping, we believed that RNA-based sequencing is the most accurate method to detected exon 14 skipping. Methods: A total of 951 NSCLC patients from two hospitals were enrolled in this study. We detected MET exon14 skipping using both targeted DNA- and RNA-based next generation sequencing and elucidated the driver gene mutation profile of Chinese NSCLC patients. Results: The overall estimated prevalence of MET exon 14 skipping was approximately 1.8% (14 of 772) in adenocarcinomas and 1.7 % (16/951) in NSCLCs. Furthermore, we compared the detection rate of MET exon 14 skipping from different specimen source, including surgical resection, percutaneous transthoracic needle biopsy (PTNB) and transbronchial lung biopsy (TBLB). Notably, the detection rate of MET exon 14 skipping from surgical resection specimen is 2.3% in NSCLCs and 2.0% in adenocarcinomas, respectively. MET exon 14 skipping was identified in 7.1% of EGFR/KRAS/ALK/ROS1/RET negative adenocarcinomas (13 of 196). In addition, PD-L1 trended to be highly expressed in NSCLC patients harboring MET exon 14 skipping (55.6% vs 17.3%, p = 0.022). Conclusions: In this study, the prevalence of MET exon14 skipping in lung adenocarcinomas in East Asian population was very close to that of West population using RNA-based NGS. The NSCLC patients with Met exon 14 skipping tended to be older than patients with other oncogenic driver mutations, such as EGFR, ALK, ROS1. In addition, PD-L1 trended to be highly expressed in NSCLC patients with MET exon 14 skipping.