Next Generation Sequencing of Chinese Stage IV Lung Cancer Patients Reveals an Association between EGFR Mutation Status and Survival Outcome

Abstract

Large-scale genomic characterization of Non-Small Cell Lung Cancer (NSCLC) has revealed several putative oncogenic driver mutations that may constitute druggable therapeutic targets. However, there are little data to suggest that such gene alterations have clinical relevance. Over 12 consecutive months, tumor biopsy samples from 80 patients with stage IV NSCLC were analyzed for mutations in selected exons of 508 cancer related genes using next generation sequencing. From 85 specimens referred for genomic characterization, 80 (94%) specimens were successfully genotyped, and all had identifiable somatic alterations. Epidermal growth factor receptor (EGFR) and TP53 genes contained the highest frequency of observed mutations (65% and 40%, respectively) in the Stage IV NSCLC cases. Notably, patients with EGFR mutations demonstrated a significantly shorter survival time compared to patients expressing wild-type EGFR (P=0.0053). Moreover, of the 32 patients harboring EGFR mutations, EGFR-L858R mutant patients demonstrated a significantly shorter survival time compared to patients with other EGFR mutations (P=0.036). In conclusion, tumors from stage IV NSCLC patients harbor characteristic gene alterations, of which EGFR L858R in particular appears to be a poor prognostic factor for overall survival.

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