TY - JOUR
T1 - Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing
AU - Liu, Pengyuan
AU - Morrison, Carl
AU - Wang, Liang
AU - Xiong, Donghai
AU - Vedell, Peter
AU - Cui, Peng
AU - Hua, Xing
AU - Ding, Feng
AU - Lu, Yan
AU - James, Michael
AU - Ebben, John D.
AU - Xu, Haiming
AU - Adjei, Alex A.
AU - Head, Karen
AU - Andrae, Jaime W.
AU - Tschannen, Michael R.
AU - Jacob, Howard
AU - Pan, Jing
AU - Zhang, Qi
AU - Van den bergh, Francoise
AU - Xiao, Haijie
AU - Lo, Ken C.
AU - Patel, Jigar
AU - Richmond, Todd
AU - Watt, Mary Anne
AU - Albert, Thomas
AU - Selzer, Rebecca
AU - Anderson, Marshall
AU - Wang, Jiang
AU - Wang, Yian
AU - Starnes, Sandra
AU - Yang, Ping
AU - You, Ming
N1 - Funding Information:
This work was supported by National Institutes of Health grants R01CA129533 (MY), R01CA113793 (MY), R01CA134682 (MY, PL), R01CA80127 (PY), R01CA84354 (PY); the Advancing a Healthier Wisconsin Chemoprevention Program (PI: MY); and the Mayo Foundation Fund (PY).
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865168855&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgs148
DO - 10.1093/carcin/bgs148
M3 - Article
C2 - 22510280
AN - SCOPUS:84865168855
SN - 0143-3334
VL - 33
SP - 1270
EP - 1276
JO - Carcinogenesis
JF - Carcinogenesis
IS - 7
ER -
