Document Detail


Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing.
MedLine Citation:
PMID:  22510280     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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 Bergh; Haijie 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
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-17
Journal Detail:
Title:  Carcinogenesis     Volume:  33     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-30     Completed Date:  2012-10-16     Revised Date:  2013-12-06    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1270-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Non-Small-Cell Lung / genetics*
Cell Line, Tumor
Exons*
Humans
Lung Neoplasms / genetics*
Mutation*
Grant Support
ID/Acronym/Agency:
R01CA113793/CA/NCI NIH HHS; R01CA129533/CA/NCI NIH HHS; R01CA134682/CA/NCI NIH HHS; R01CA80127/CA/NCI NIH HHS; R01CA84354/CA/NCI NIH HHS; T32 GM080202/GM/NIGMS NIH HHS
Comments/Corrections

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