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Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing. Carcinogenesis 2012 Jul;33(7):1270-6 PMID: 22510280 PMCID: PMC3499051

Pubmed ID

22510280

DOI

10.1093/carcin/bgs148

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.

Author List

Liu P, Morrison C, Wang L, Xiong D, Vedell P, Cui P, Hua X, Ding F, Lu Y, James M, Ebben JD, Xu H, Adjei AA, Head K, Andrae JW, Tschannen MR, Jacob H, Pan J, Zhang Q, Van den Bergh F, Xiao H, Lo KC, Patel J, Richmond T, Watt MA, Albert T, Selzer R, Anderson M, Wang J, Wang Y, Starnes S, Yang P, You M

Authors

Michael James PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Pengyuan Liu PhD Adjunct Associate Professor in the Physiology department at Medical College of Wisconsin
Jing Pan PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Liang Wang MD, PhD Professor in the Pathology department at Medical College of Wisconsin
Yian Wang MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Qi Zhang PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-84865168855   116 Citations

MESH terms used to index this publication - Major topics in bold

Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Exons
Humans
Lung Neoplasms
Mutation
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e