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Assessment of Nine Driver Gene Mutations in Surgically Resected Samples from Patients with Non-Small-Cell Lung Cancer

Authors Wang S, Qu X, Cao L, Hu X, Hou K, Liu Y, Che X

Received 22 February 2020

Accepted for publication 13 May 2020

Published 28 May 2020 Volume 2020:12 Pages 4029—4038

DOI https://doi.org/10.2147/CMAR.S250822

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Shuo Wang,1– 3 Xiujuan Qu,1– 3 Lili Cao,1– 3 Xuejun Hu,4 Kezuo Hou,1– 3 Yunpeng Liu,1– 3 Xiaofang Che1– 3

1Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 3Liaoning Province Clinical Research Center for Cancer, Shenyang 110001, People’s Republic of China; 4Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China

Correspondence: Xiaofang Che; Xiujuan Qu Email xfche@cmu.edu.cn; xiujuanqu@yahoo.com

Background: The mutational profile of oncogenic driver genes play an important role in non-small-cell lung cancer (NSCLC). The need of a testing panel capable of comprehensively determining patient genotypes in limited amounts of material has increased since the recent association of nine core oncogenic driver genes as tumor predictive biomarkers.
Methods: Surgically resected samples from 214 NSCLC patients (168 patients with adenocarcinomas and 46 with squamous cell cancers) were included. A multiplexed PCR-based assay was developed to simultaneously test 118 hotspot mutations and fusions in nine driver genes.
Results: The sensitivity of the kit was 1% for gene mutation and 450 copies for gene fusion. Genetic alterations were detected in 143 (66.8%) patients by the assay. The three most common alterations identified were EGFR mutations (50.9%), KRAS mutations (8.4%) and ALK fusions (4.7%). Eight (3.7%) patients harbored concurrent mutations, and the most common partners were EGFR mutations which were observed in the eight patients. No associations between survival and EGFR, KRAS, and ALK status were observed. Patients with two or more alterations exhibited shorter DFS compared to those with single mutations (P=0.032), whilst had no significant difference in OS (P=0.245). However, only TNM stage was an independent predictor of OS (HR=2.905, P< 0.001) as well as DFS (HR=2.114, P< 0.001) in our cohort in multivariate analysis. Furthermore, patients with the L858R mutation had longer DFS (P=0.014) compared to other sensitizing mutations and tended to have better OS but the differences were not significant (P=0.06).
Conclusion: These findings suggest this multiplex gene panel testing technique can be efficiently used to detect nine driver genes in a limited number of specimens. This methodology would have the potential to save both specimens and time compared to the combination of all assays by other methods.

Keywords: drive gene, lung cancer, multi-mutational profiling, prognosis

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