Circulating Tumor DNA-Based Next-Generation Sequencing Uncovers Tumor-Associated Gene Mutation Profiles in NSCLC Patients With and Without Treatment

Xie Yunxia Wang Xiaonan Li Guangqi Ran Wenwen Xing Xiaoming ^*

• The Affiliated Hospital of Qingdao University, Qingdao, China

Background: CirculatingPlasma freetumor DNA (ctDNA) sequencing is used to detect tumor-related gene mutations in patients with advanced non-small cell lung cancer (NSCLC) where tumor tissue was difficult to obtaindifficulty obtained. The aim of this study was to determine the genomic variation profiles of real-world Chinese NSCLC patients with or without treatment and to identify NSCLC patients without treatment suitable for ctDNA sequencing.Methods: A total of 132 patients who diagnosed with NSCLC were enrolled and received ctDNA-based next-generation sequencing (NGS). NGS analysis was carried out using a 196-gene panel on NextSeq TM 550Dx platform. Patients were divided into three groups according to whether they used targeted drugs, chemotherapy drugs or no drugs prior to sequencing according to the clinical information collected. The genomic profiles and the clinical characteristics were demonstrated using waterfall plot.Results: 107 patients (81.1%) were detected with at least one mutation, including single-base variant, base deletion and gene amplification, but no significant association was found between mutation status and several clinical features. In the targeted therapy group, the EGFR mutation rate was highest (52%). DNMT3A was the most commonly mutated gene in the chemotherapy group (27%), and the TP53 mutation rate was highest in the untreated group (42%). In the targeted therapy group, there was also a relatively wider distribution of EGFR mutation sites (exon 8-exon 21), and both EGFR-targeted drug-sensitive and drug-resistant sites were present in several samples. In the untreated group, EGFR mutations were exclusively found in female lung adenocarcinoma patientsEGFR mutations were only found in female lung adenocarcinoma patients.ctDNA-based NGS in NSCLC patients receiving targeted therapies reveals the evolution of tumor cells under the stress of drugs. For female lung adenocarcinoma patients with inaccessible tissue, ctDNA-based sequencing may be recommended routinely.