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Research Paper|Volume 12, Issue 13|pp 13701—13715

Exome sequencing identifies somatic mutations in novel driver genes in non-small cell lung cancer

Manman Zhang1,2, Lele Zhang3, Yan Li1, Feng Sun1, Ya Fang1, Ruijia Zhang1, Jin Wu1, Guanbiao Zhou4, Huaidong Song1, Liqiong Xue5, Bing Han2, Cuixia Zheng6
  • 1Clinical Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 2Department of Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 3Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 4State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  • 5Department of Oncology, Dongfang Hospital, Tongji University School of Medicine, Shanghai, China
  • 6Department of Respiration, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
* Equal contribution
Received: February 27, 2020Accepted: May 27, 2020Published: July 6, 2020
https://doi.org/10.18632/aging.103500

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Lung cancer is the leading cause of cancer death worldwide and accounts for more than one-third of all newly diagnosed cancer cases in China. Therefore, it is of great clinical significance to explore new driver gene mutations in non-small-cell lung cancer (NSCLC). Using an initial bioinformatic analysis, we identified somatic gene mutations in 13 patients with NSCLC and confirmed these mutations by targeted sequencing in an extended validation group of 88 patients. Recurrent mutations were detected in UNC5D (7.9%), PREX1 (5.0%), HECW1 (4.0%), DACH1 (2.0%), and GPC5 (2.0%). A functional study was also performed in UNC5D mutants. Mutations in UNC5D promoted tumorigenesis by abolishing the tumor suppressor function of the encoded protein. Additionally, in ten patients with lung squamous cell carcinoma, we identified mutations in KEAP1/NFE2L2 that influenced the expression of target genes in vivo and in vitro. Overall, the results of our study expanded the known spectrum of driver mutations involved in the pathogenesis of NSCLC.