Sequential Whole Exome Sequencing Reveals Somatic Mutations Associated with Platinum Response in NSCLC

Release time:2023-02-13

Impact Factor:4.345

DOI number:10.2147/OTT.S254747

Affiliation of Author(s):Xiangya Hospital, Central South University

Teaching and Research Group:Department of Clinical Pharmacology

Journal:OncoTargets and Therapy

Funded by:National Natural Science Foundation of China (81773823, 81573463,81641039,81571151）

Key Words:NSCLC; TP53; TTN; cfDNA; platinum.

Abstract:Purpose: Resistance is one of the main limitations of successful platinum treatment in non-small-cell lung cancer (NSCLC) patients. In this study, we aimed to identify somatic mutations associated with platinum response. Patients and methods: A total of 57 patients who received platinum-based chemotherapy only and 13 patients who received neoadjuvant chemotherapy (NAC) were enrolled. Somatic mutations were obtained from targeted and whole exome sequencing (WES). Results: Somatic mutations in a total of 225 genes were observed. Nonsynonymous variants in EGFR, TTN, TP53 and KRAS, and copy number variations (SCNVs) in chromosome 8q24.3 and 22q11.21 were identified to be associated with platinum response. Based on these mutations, the mutational signature associated with the failure of DNA double-strand break and calcium signaling pathways were identified to be associated with platinum response. Besides, we observed a decrease in tumor mutational burden after chemotherapy. We also evaluated the mutation spectrum consistency between cell-free DNA (cfDNA) and tissue DNA. Somatic mutations detected in cfDNA were consistent with that in tDNA, which indicated that plasma might be used for somatic mutation detection. Conclusion: These results support that somatic mutations can affect platinum drug response and provide potential clinical biomarkers for NSCLC treatment.

Co-author:Fan Xiao, Wei-Hua Shao, Yan Zhan, Le Zhang, Jing Xiong, Yang Gao, Ji-Ye Yin

First Author:Ao-Xiang Guo

Indexed by:Journal paper

Discipline:Medicine

First-Level Discipline:Pharmaceutical Science

Document Type:J

Volume:13

Page Number:6485-6496

Number of Words:6077

ISSN No.:1178-6930

Translation or Not:no

Date of Publication:2020-07-03

Included Journals:SCI

Links to published journals:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342605/