Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing

被引：1506

作者：

Imielinski, Marcin ^{[1
,2
,3
,5
]}

Berger, Alice H. ^{[1
,5
]}

Hammerman, Peter S. ^{[1
,5
]}

Hernandez, Bryan ^{[1
]}

Pugh, Trevor J. ^{[1
,5
]}

Hodis, Eran ^{[1
]}

Cho, Jeonghee ^{[6
]}

Suh, James ^{[7
]}

Capelletti, Marzia ^{[5
]}

Sivachenko, Andrey ^{[1
]}

Sougnez, Carrie ^{[1
]}

Auclair, Daniel ^{[1
]}

Lawrence, Michael S. ^{[1
]}

Stojanov, Petar ^{[1
,5
]}

Cibulskis, Kristian ^{[1
]}

Choi, Kyusam ^{[6
]}

de Waal, Luc ^{[1
,5
]}

Sharifnia, Tanaz ^{[1
,5
]}

Brooks, Angela ^{[1
,5
]}

Greulich, Heidi ^{[1
,5
]}

Banerji, Shantanu ^{[1
,5
]}

Zander, Thomas ^{[9
,10
,12
]}

Seidel, Danila ^{[9
,10
]}

Leenders, Frauke ^{[9
,10
]}

Ansen, Sascha ^{[9
,10
]}

Ludwig, Corinna ^{[9
,10
]}

Engel-Riedel, Walburga ^{[9
,10
]}

Stoelben, Erich ^{[9
,10
]}

Wolf, Juergen ^{[9
,10
]}

Goparju, Chandra ^{[8
]}

Thompson, Kristin ^{[1
]}

Winckler, Wendy ^{[1
]}

Kwiatkowski, David ^{[5
]}

Johnson, Bruce E. ^{[5
]}

Jaenne, Pasi A. ^{[5
]}

Miller, Vincent A. ^{[13
]}

Pao, William ^{[15
]}

Travis, William D. ^{[14
]}

Pass, Harvey I. ^{[8
]}

Gabriel, Stacey B. ^{[1
]}

Lander, Eric S. ^{[1
,4
,16
]}

Thomas, Roman K. ^{[9
,10
,11
,12
,17
,18
]}

Garraway, Levi A. ^{[1
,5
]}

Getz, Gad ^{[1
]}

Meyerson, Matthew ^{[1
,3
,5
]}

机构：

[1] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[2] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[6] Samsung Med Ctr, Samsung Res Inst, Seoul 135967, South Korea

[7] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10016 USA

[8] NYU, Langone Med Ctr, Dept Cardiothorac Surg, New York, NY 10016 USA

[9] Univ Cologne, Dept Internal Med, D-50924 Cologne, Germany

[10] Univ Cologne, Ctr Integrated Oncol, D-50924 Cologne, Germany

[11] Univ Cologne, Lab Translat Canc Genom Koln Bonn, D-50924 Cologne, Germany

[12] Max Planck Inst Neurol Res, D-50924 Cologne, Germany

[13] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10065 USA

[14] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[15] Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, Nashville, TN 37232 USA

[16] MIT, Dept Biol, Cambridge, MA 02142 USA

[17] Univ Cologne, Dept Translat Genom, D-50931 Cologne, Germany

[18] Univ Cologne, Dept Pathol, D-50937 Cologne, Germany

来源：

CELL | 2012年 / 150卷 / 06期

关键词：

GROWTH-FACTOR RECEPTOR; SOMATIC MUTATIONS; GENE-MUTATIONS; CANCER; GENOME; EGFR; LANDSCAPE; GEFITINIB; PATTERNS; REVEALS;

D O I：

10.1016/j.cell.2012.08.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1107 / 1120

页数：14

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