Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 2012 Sep 14;150(6):1121-34
Date
09/18/2012Pubmed ID
22980976Pubmed Central ID
PMC3656590DOI
10.1016/j.cell.2012.08.024Scopus ID
2-s2.0-84866434919 (requires institutional sign-in at Scopus site) 1023 CitationsAbstract
We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs.
Author List
Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RKMESH terms used to index this publication - Major topics in bold
Carcinoma, Non-Small-Cell LungChromosome Aberrations
Female
Gene Expression Profiling
Genome-Wide Association Study
High-Throughput Nucleotide Sequencing
Humans
INDEL Mutation
Lung Neoplasms
Male
Molecular Targeted Therapy
Point Mutation
Smoking
