Mutation Spectrum of From 21,324 Chinese Patients With Non-Small Cell Lung Cancer (NSCLC) Successfully Tested by Multiple Methods in a CAP-Accredited Laboratory.

Genotyping epidermal growth factor receptor () gene in patients with advanced non-small cell lung cancers (NSCLC) is essential for identifying those patients who may benefit from targeted therapies. Systemically evaluating mutation detection rates of different methods currently used in clinical setting will provide valuable information to clinicians and laboratory scientists who take care of NSCLC patients. This study retrospectively reviewed the data obtained in our laboratory in last 10 years. A total of 21,324 NSCLC cases successfully underwent genotyping for clinical therapeutic purpose, including 5,244 cases tested by Sanger sequencing, 13,329 cases tested by real-time PCR, and 2,751 tested by next-generation sequencing (NGS). The average mutation rate was 45.1%, with 40.3% identified by Sanger sequencing, 46.5% by real-time PCR and 47.5% by NGS. Of these cases with mutations identified, 93.3% of them harbored a single mutation (92.1% with 19del or L858R, and 7.9% with uncommon mutations) and 6.7% harbored complex mutations. Of the 72 distinct variants identified in this study, 15 of them (single or complex mutations) were newly identified in NSCLC. For these cases with mutations tested by NGS, 65.3% of them also carried tumor-related variants in some non- genes and about one third of them were considered candidates of targeted drugs. NGS method showed advantages over Sanger sequencing and real-time PCR not only by providing the highest mutation detection rate of but also by identifying actionable non- mutations with targeted drugs in clinical setting.