Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing | Zendy

Marcin Imieliński | Zendy; Alice H. Berger | Zendy; Peter S. Hammerman | Zendy; Bryan Hernandez | Zendy; Trevor J. Pugh | Zendy; Eran Hodis | Zendy; Jeonghee Cho | Zendy; James Suh | Zendy; Marzia Capelletti | Zendy; Andrey Sivachenko | Zendy; Carrie Sougnez | Zendy; Daniel Auclair | Zendy; Michael S. Lawrence | Zendy; Petar Stojanov | Zendy; Kristian Cibulskis | Zendy; Kyusam Choi | Zendy; Luc de Waal | Zendy; Tanaz Sharifnia | Zendy; Angela N. Brooks | Zendy; Heidi Greulich | Zendy; Shantanu Banerji | Zendy; Thomas Zander | Zendy; Danila Seidel | Zendy; Frauke Leenders | Zendy; Sascha Ansén | Zendy; Corinna Ludwig | Zendy; Walburga Engel-Riedel | Zendy; Erich Stoelben | Zendy; Jürgen Wolf | Zendy; Chandra Goparju | Zendy; Kristin Thompson | Zendy; Wendy Winckler | Zendy; David J. Kwiatkowski | Zendy; Bruce E. Johnson | Zendy; Pasi A. Jänne | Zendy; Vincent A. Miller | Zendy; William Pao | Zendy; William D. Travis | Zendy; Harvey I. Pass | Zendy; Stacey Gabriel | Zendy; Eric S. Lander | Zendy; Roman K. Thomas | Zendy; Levi A. Garraway | Zendy; Gad Getz | Zendy; Matthew Meyerson | Zendy

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Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing

Author(s) -

Marcin Imieliński,

Alice H. Berger,

Peter S. Hammerman,

Bryan Hernandez,

Trevor J. Pugh,

Eran Hodis,

Jeonghee Cho,

James Suh,

Marzia Capelletti,

Andrey Sivachenko,

Carrie Sougnez,

Daniel Auclair,

Michael S. Lawrence,

Petar Stojanov,

Kristian Cibulskis,

Kyusam Choi,

Luc de Waal,

Tanaz Sharifnia,

Angela N. Brooks,

Heidi Greulich,

Shantanu Banerji,

Thomas Zander,

Danila Seidel,

Frauke Leenders,

Sascha Ansén,

Corinna Ludwig,

Walburga Engel-Riedel,

Erich Stoelben,

Jürgen Wolf,

Chandra Goparju,

Kristin Thompson,

Wendy Winckler,

David J. Kwiatkowski,

Bruce E. Johnson,

Pasi A. Jänne,

Vincent A. Miller,

William Pao,

William D. Travis,

Harvey I. Pass,

Stacey Gabriel,

Eric S. Lander,

Roman K. Thomas,

Levi A. Garraway,

Gad Getz,

Matthew Meyerson

Publication year - 2012

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2012.08.029

Subject(s) - biology , adenocarcinoma , exome sequencing , genetics , gene , lung cancer , mutation , exome , somatic cell , context (archaeology) , arid1a , germline mutation , cancer research , cancer , pathology , medicine , paleontology

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.

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