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Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.


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.

SUBMITTER: Imielinski M 

PROVIDER: S-EPMC3557932 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.

Imielinski Marcin M   Berger Alice H AH   Hammerman Peter S PS   Hernandez Bryan B   Pugh Trevor J TJ   Hodis Eran E   Cho Jeonghee J   Suh James J   Capelletti Marzia M   Sivachenko Andrey A   Sougnez Carrie C   Auclair Daniel D   Lawrence Michael S MS   Stojanov Petar P   Cibulskis Kristian K   Choi Kyusam K   de Waal Luc L   Sharifnia Tanaz T   Brooks Angela A   Greulich Heidi H   Banerji Shantanu S   Zander Thomas T   Seidel Danila D   Leenders Frauke F   Ansén Sascha S   Ludwig Corinna C   Engel-Riedel Walburga W   Stoelben Erich E   Wolf Jürgen J   Goparju Chandra C   Thompson Kristin K   Winckler Wendy W   Kwiatkowski David D   Johnson Bruce E BE   Jänne Pasi A PA   Miller Vincent A VA   Pao William W   Travis William D WD   Pass Harvey I HI   Gabriel Stacey B SB   Lander Eric S ES   Thomas Roman K RK   Garraway Levi A LA   Getz Gad G   Meyerson Matthew M  

Cell 20120901 6


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  ...[more]

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