title: Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing.
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.
authors.affiliation: Department of Physiology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Liu
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Donghai
authors.initials: D
authors.lastname: Xiong
authors.forename: Peter
authors.initials: P
authors.lastname: Vedell
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.forename: Xing
authors.initials: X
authors.lastname: Hua
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: James
authors.forename: John D
authors.initials: JD
authors.lastname: Ebben
authors.forename: Haiming
authors.initials: H
authors.lastname: Xu
authors.forename: Alex A
authors.initials: AA
authors.lastname: Adjei
authors.forename: Karen
authors.initials: K
authors.lastname: Head
authors.forename: Jaime W
authors.initials: JW
authors.lastname: Andrae
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tschannen
authors.forename: Howard
authors.initials: H
authors.lastname: Jacob
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Francoise
authors.initials: F
authors.lastname: Van den Bergh
authors.forename: Haijie
authors.initials: H
authors.lastname: Xiao
authors.forename: Ken C
authors.initials: KC
authors.lastname: Lo
authors.forename: Jigar
authors.initials: J
authors.lastname: Patel
authors.forename: Todd
authors.initials: T
authors.lastname: Richmond
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Watt
authors.forename: Thomas
authors.initials: T
authors.lastname: Albert
authors.forename: Rebecca
authors.initials: R
authors.lastname: Selzer
authors.forename: Marshall
authors.initials: M
authors.lastname: Anderson
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Sandra
authors.initials: S
authors.lastname: Starnes
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D005091:Exons; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation