Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.

Cell
Authors
Keywords
Abstract

Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for more than 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. Whole-genome sequence analysis revealed frequent structural rearrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. The candidate genes identified in this study are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma.

Year of Publication
2012
Journal
Cell
Volume
150
Issue
6
Pages
1107-20
Date Published
2012 Sep 14
ISSN
1097-4172
URL
DOI
10.1016/j.cell.2012.08.029
PubMed ID
22980975
PubMed Central ID
PMC3557932
Links
Grant list
U54 HG003067 / HG / NHGRI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
T32GM07753 / GM / NIGMS NIH HHS / United States
R01 CA109038 / CA / NCI NIH HHS / United States
Canadian Institutes of Health Research / Canada
T32 CA009216 / CA / NCI NIH HHS / United States
T32 CA9216 / CA / NCI NIH HHS / United States
P50 CA090578 / CA / NCI NIH HHS / United States
R01 CA116020 / CA / NCI NIH HHS / United States