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Authors Cao L, Long L, Li M, Yang H, Deng P, Mao X, Xiang J, Li B, Zhang T, Hu C
Received 3 November 2017
Accepted for publication 10 January 2018
Published 8 May 2018 Volume 2018:11 Pages 2637—2646
DOI https://doi.org/10.2147/OTT.S155995
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 4
Editor who approved publication: Dr William Cho
Purpose: The development of next-generation sequencing (NGS) has revolutionized
the understanding of oncogenesis of multiple types of cancer, including
non-small cell lung cancer (NSCLC). However, there has been some debate over
the utility of NGS for predicting patient prognosis and determining molecular
targeted therapy. Therefore, we sought to demonstrate the numerous applications
of NGS in the prognostic predictions and treatment of NSCLC patients.
Materials and
methods: We performed NGS on either
liquid or tissue tumor biopsies obtained from 53 NSCLC patients. The sequences
were analyzed for oncogenic mutations, which were then correlated to clinical
prognosis and smoking history.
Results: NGS of tumor biopsies detected both well-known driver mutations as well
as rare or novel mutations. EGFR was the
most frequently mutated gene, accounting for 32.4% (33/102) of the somatic
mutations in this study. The EGFR mutations
detected included rare variants such as EGFR exon 19
insertion (K745_E746insIPVAIK) and in cis H835L+L833V.
Additionally, novel RET fusion
mutations PCM1–RET and ADD3-RET were detected in two
adenocarcinoma patients. To demonstrate the functional applications of NGS, we
correlated mutations with patient characteristics, outcomes of matched targeted
therapy, and outcomes based on allelic frequency of the EGFR -T790M mutation. Finally, we
demonstrated that circulating tumor DNA can be used both to measure response to
targeted therapy and as a predictor of clinical outcome, by presenting a case
study of a single patient.
Conclusion: We demonstrated that NGS can be used in multiple applications to
effectively identify potential oncogenic driver mutations, guide
mutation-targeted therapy decisions, and predict clinical outcomes in Chinese
NSCLC patients.
Keywords: next-generation sequencing, non-small cell lung cancer, prognosis