Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing

Pengyuan Liu, Carl Morrison, Liang Wang, Donghai Xiong, Peter Vedell, Peng Cui, Xing Hua, Feng Ding, Yan Lu, Michael James, John D. Ebben, Haiming Xu, Alex A. Adjei, Karen Head, Jaime W. Andrae, Michael R. Tschannen, Howard Jacob, Jing Pan, Qi Zhang, Francoise Van den berghHaijie Xiao, Ken C. Lo, Jigar Patel, Todd Richmond, Mary Anne Watt, Thomas Albert, Rebecca Selzer, Marshall Anderson, Jiang Wang, Yian Wang, Sandra Starnes, Ping Yang, Ming You

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Lung cancer is the leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) being the predominant form of the disease. Most lung cancer is caused by the accumulation of genomic alterations due to tobacco exposure. To uncover its mutational landscape, we performed whole-exome sequencing in 31 NSCLCs and their matched normal tissue samples. We identified both common and unique mutation spectra and pathway activation in lung adenocarcinomas and squamous cell carcinomas, two major histologies in NSCLC. In addition to identifying previously known lung cancer genes (TP53, KRAS, EGFR, CDKN2A and RB1), the analysis revealed many genes not previously implicated in this malignancy. Notably, a novel gene CSMD3 was identified as the second most frequently mutated gene (next to TP53) in lung cancer. We further demonstrated that loss of CSMD3 results in increased proliferation of airway epithelial cells. The study provides unprecedented insights into mutational processes, cellular pathways and gene networks associated with lung cancer. Of potential immediate clinical relevance, several highly mutated genes identified in our study are promising druggable targets in cancer therapy including ALK, CTNNA3, DCC, MLL3, PCDHIIX, PIK3C2B, PIK3CG and ROCK2.

Original languageEnglish (US)
Pages (from-to)1270-1276
Number of pages7
JournalCarcinogenesis
Volume33
Issue number7
DOIs
StatePublished - Jul 1 2012

ASJC Scopus subject areas

  • Cancer Research

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    Liu, P., Morrison, C., Wang, L., Xiong, D., Vedell, P., Cui, P., Hua, X., Ding, F., Lu, Y., James, M., Ebben, J. D., Xu, H., Adjei, A. A., Head, K., Andrae, J. W., Tschannen, M. R., Jacob, H., Pan, J., Zhang, Q., ... You, M. (2012). Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing. Carcinogenesis, 33(7), 1270-1276. https://doi.org/10.1093/carcin/bgs148