Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing

被引：1500

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

共 56 条

[11] Cancer Genome Atlas Research Network, 2012, NATURE
[12] Initial genome sequencing and analysis of multiple myeloma
Chapman, Michael A.
Lawrence, Michael S.
Keats, Jonathan J.
Cibulskis, Kristian
Sougnez, Carrie
Schinzel, Anna C.
Harview, Christina L.
Brunet, Jean-Philippe
Ahmann, Gregory J.
Adli, Mazhar
Anderson, Kenneth C.
Ardlie, Kristin G.
Auclair, Daniel
Baker, Angela
Bergsagel, P. Leif
Bernstein, Bradley E.
Drier, Yotam
Fonseca, Rafael
Gabriel, Stacey B.
Hofmeister, Craig C.
Jagannath, Sundar
Jakubowiak, Andrzej J.
Krishnan, Amrita
Levy, Joan
Liefeld, Ted
Lonial, Sagar
Mahan, Scott
Mfuko, Bunmi
Monti, Stefano
Perkins, Louise M.
Onofrio, Robb
Pugh, Trevor J.
Rajkumar, S. Vincent
Ramos, Alex H.
Siegel, David S.
Sivachenko, Andrey
Stewart, A. Keith
Trudel, Suzanne
Vij, Ravi
Voet, Douglas
Winckler, Wendy
Zimmerman, Todd
Carpten, John
Trent, Jeff
Hahn, William C.
Garraway, Levi A.
Meyerson, Matthew
Lander, Eric S.
Getz, Gad
Golub, Todd R.
[J]. NATURE, 2011, 471 (7339) : 467 - 472
[13] Glioblastoma-Derived Epidermal Growth Factor Receptor Carboxyl-Terminal Deletion Mutants Are Transforming and Are Sensitive to EGFR-Directed Therapies
Cho, Jeonghee
Pastorino, Sandra
Zeng, Qing
Xu, Xiaoyin
Johnson, William
Vandenberg, Scott
Verhaak, Roel
Cherniack, Andrew D.
Watanabe, Hideo
Dutt, Amit
Kwon, Jihyun
Chao, Ying S.
Onofrio, Robert C.
Chiang, Derek
Yuza, Yuki
Kesari, Santosh
Meyerson, Matthew
[J]. CANCER RESEARCH, 2011, 71 (24) : 7587 - 7596
[14] Somatic mutations affect key pathways in lung adenocarcinoma
Ding, Li
Getz, Gad
Wheeler, David A.
Mardis, Elaine R.
McLellan, Michael D.
Cibulskis, Kristian
Sougnez, Carrie
Greulich, Heidi
Muzny, Donna M.
Morgan, Margaret B.
Fulton, Lucinda
Fulton, Robert S.
Zhang, Qunyuan
Wendl, Michael C.
Lawrence, Michael S.
Larson, David E.
Chen, Ken
Dooling, David J.
Sabo, Aniko
Hawes, Alicia C.
Shen, Hua
Jhangiani, Shalini N.
Lewis, Lora R.
Hall, Otis
Zhu, Yiming
Mathew, Tittu
Ren, Yanru
Yao, Jiqiang
Scherer, Steven E.
Clerc, Kerstin
Metcalf, Ginger A.
Ng, Brian
Milosavljevic, Aleksandar
Gonzalez-Garay, Manuel L.
Osborne, John R.
Meyer, Rick
Shi, Xiaoqi
Tang, Yuzhu
Koboldt, Daniel C.
Lin, Ling
Abbott, Rachel
Miner, Tracie L.
Pohl, Craig
Fewell, Ginger
Haipek, Carrie
Schmidt, Heather
Dunford-Shore, Brian H.
Kraja, Aldi
Crosby, Seth D.
Sawyer, Christopher S.
[J]. NATURE, 2008, 455 (7216) : 1069 - 1075
[15] AMPLIFIED AND REARRANGED EPIDERMAL GROWTH-FACTOR RECEPTOR GENES IN HUMAN GLIOBLASTOMAS REVEAL DELETIONS OF SEQUENCES ENCODING PORTIONS OF THE N-TERMINAL AND OR C-TERMINAL TAILS
EKSTRAND, AJ
SUGAWA, N
JAMES, CD
COLLINS, VP
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) : 4309 - 4313
[16] New Epigenetic Drivers of Cancers
Elsaesser, Simon J.
Allis, C. David
Lewis, Peter W.
[J]. SCIENCE, 2011, 331 (6021) : 1145 - 1146
[17] A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries
Fisher, Sheila
Barry, Andrew
Abreu, Justin
Minie, Brian
Nolan, Jillian
Delorey, Toni M.
Young, Geneva
Fennell, Timothy J.
Allen, Alexander
Ambrogio, Lauren
Berlin, Aaron M.
Blumenstiel, Brendan
Cibulskis, Kristian
Friedrich, Dennis
Johnson, Ryan
Juhn, Frank
Reilly, Brian
Shammas, Ramy
Stalker, John
Sykes, Sean M.
Thompson, Jon
Walsh, John
Zimmer, Andrew
Zwirko, Zac
Gabriel, Stacey
Nicol, Robert
Nusbaum, Chad
[J]. GENOME BIOLOGY, 2011, 12 (01):
[18] COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, Simon A.
Bindal, Nidhi
Bamford, Sally
Cole, Charlotte
Kok, Chai Yin
Beare, David
Jia, Mingming
Shepherd, Rebecca
Leung, Kenric
Menzies, Andrew
Teague, Jon W.
Campbell, Peter J.
Stratton, Michael R.
Futreal, P. Andrew
[J]. NUCLEIC ACIDS RESEARCH, 2011, 39 : D945 - D950
[19] A census of human cancer genes
Futreal, PA
Coin, L
Marshall, M
Down, T
Hubbard, T
Wooster, R
Rahman, N
Stratton, MR
[J]. NATURE REVIEWS CANCER, 2004, 4 (03) : 177 - 183
[20] Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, Marco
Rowan, Andrew J.
Horswell, Stuart
Larkin, James
Endesfelder, David
Gronroos, Eva
Martinez, Pierre
Matthews, Nicholas
Stewart, Aengus
Tarpey, Patrick
Varela, Ignacio
Phillimore, Benjamin
Begum, Sharmin
McDonald, Neil Q.
Butler, Adam
Jones, David
Raine, Keiran
Latimer, Calli
Santos, Claudio R.
Nohadani, Mahrokh
Eklund, Aron C.
Spencer-Dene, Bradley
Clark, Graham
Pickering, Lisa
Stamp, Gordon
Gore, Martin
Szallasi, Zoltan
Downward, Julian
Futreal, P. Andrew
Swanton, Charles
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (10) : 883 - 892

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