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

Aging (Albany NY). 2020 Jul 6;12(13):13701-13715. doi: 10.18632/aging.103500. Epub 2020 Jul 6.

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.

Keywords: UNC5D; driver gene mutation; exome sequencing; non-small-cell lung cancer.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Case-Control Studies
  • Computational Biology
  • DNA Mutational Analysis
  • Exome Sequencing
  • Humans
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Mice
  • Middle Aged
  • Mutation
  • Pneumonectomy
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor