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Cell DOI:10.1016/j.cell.2012.08.029

Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.

Publication TypeJournal Article
Year of Publication2012
AuthorsImielinski, M, Berger, AH, Hammerman, PS, Hernandez, B, Pugh, TJ, Hodis, E, Cho, J, Suh, J, Capelletti, M, Sivachenko, A, Sougnez, C, Auclair, D, Lawrence, MS, Stojanov, P, Cibulskis, K, Choi, K, de Waal, L, Sharifnia, T, Brooks, A, Greulich, H, Banerji, S, Zander, T, Seidel, D, Leenders, F, Ansén, S, Ludwig, C, Engel-Riedel, W, Stoelben, E, Wolf, J, Goparju, C, Thompson, K, Winckler, W, Kwiatkowski, D, Johnson, BE, Jänne, PA, Miller, VA, Pao, W, Travis, WD, Pass, HI, Gabriel, SB, Lander, ES, Thomas, RK, Garraway, LA, Getz, G, Meyerson, M
JournalCell
Volume150
Issue6
Pages1107-20
Date Published2012 Sep 14
ISSN1097-4172
KeywordsAdenocarcinoma, Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Cohort Studies, Exome, Female, Genes, Neoplasm, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Mutation Rate
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0092-8674(12)01061-6
DOI10.1016/j.cell.2012.08.029
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22980975?dopt=Abstract

Alternate JournalCell
PubMed ID22980975
PubMed Central IDPMC3557932
Grant ListU54 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