The landscape of somatic copy-number alteration across human cancers

被引：3030

作者：

Beroukhim, Rameen ^{[1
,2
,4
,5
,6
,7
,8
,9
,10
,11
,12
,13
]}

Mermel, Craig H. ^{[1
,2
,4
,5
,6
,7
]}

Porter, Dale ^{[16
]}

Wei, Guo ^{[1
,2
]}

Raychaudhuri, Soumya ^{[1
,2
,8
,9
]}

Donovan, Jerry ^{[16
]}

Barretina, Jordi ^{[1
,2
,4
,5
,6
,7
]}

Boehm, Jesse S. ^{[1
,2
]}

Dobson, Jennifer ^{[1
,2
,4
,5
,6
,7
]}

Urashima, Mitsuyoshi ^{[17
]}

Mc Henry, Kevin T. ^{[16
]}

Pinchback, Reid M. ^{[1
,2
]}

Ligon, Azra H. ^{[8
,9
]}

Cho, Yoon-Jae ^{[14
]}

Haery, Leila ^{[1
,2
,4
,5
,6
,7
]}

Greulich, Heidi ^{[1
,2
,4
,5
,6
,7
,8
,9
,10
,11
,12
,13
]}

Reich, Michael ^{[1
,2
]}

Winckler, Wendy ^{[1
,2
]}

Lawrence, Michael S. ^{[1
,2
]}

Weir, Barbara A. ^{[1
,2
,4
,5
,6
,7
]}

Tanaka, Kumiko E. ^{[1
,2
,4
,5
,6
,7
]}

Chiang, Derek Y. ^{[1
,2
,4
,5
,6
,7
,22
]}

Bass, Adam J. ^{[1
,2
,4
,5
,6
,7
,8
,9
]}

Loo, Alice ^{[16
]}

Hoffman, Carter ^{[1
,2
,4
,5
,6
,7
]}

Prensner, John ^{[1
,2
,4
,5
,6
,7
]}

Liefeld, Ted ^{[1
,2
]}

Gao, Qing ^{[1
,2
]}

Yecies, Derek ^{[4
,5
,6
,7
]}

Signoretti, Sabina ^{[4
,5
,6
,7
,8
,9
]}

Maher, Elizabeth ^{[18
]}

Kaye, Frederic J. ^{[19
,20
]}

Sasaki, Hidefumi ^{[21
]}

Tepper, Joel E. ^{[22
]}

Fletcher, Jonathan A. ^{[8
,9
]}

Tabernero, Josep ^{[23
,24
]}

Baselga, Jose ^{[23
,24
]}

Tsao, Ming-Sound ^{[25
,26
,27
]}

Demichelis, Francesca ^{[28
]}

Rubin, Mark A. ^{[28
]}

Janne, Pasi A. ^{[4
,5
,6
,7
,8
,9
]}

Daly, Mark J. ^{[1
,2
,29
]}

Nucera, Carmelo ^{[15
]}

Levine, Ross L. ^{[30
,31
]}

Ebert, Benjamin L. ^{[1
,2
,8
,9
,10
,11
,12
,13
]}

Gabriel, Stacey ^{[1
,2
]}

Rustgi, Anil K. ^{[32
,33
,34
]}

Antonescu, Cristina R. ^{[30
,31
]}

Ladanyi, Marc ^{[30
,31
]}

Letai, Anthony ^{[4
,5
,6
,7
]}

机构：

[1] Broad Inst MIT & Harvard, Canc Program, Cambridge Ctr 7, Cambridge, MA 02142 USA

[2] Broad Inst MIT & Harvard, Med & Populat Genet Grp, Cambridge Ctr 7, Cambridge, MA 02142 USA

[3] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA

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

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

[6] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[7] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[8] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[9] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

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

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

[12] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

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

[14] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA

[15] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA

[16] Novartis Inst BioMed Res, Cambridge, MA 02139 USA

[17] Jikei Univ, Sch Med, Div Mol Epidemiol, Minato Ku, Tokyo 1058461, Japan

[18] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

[19] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20889 USA

[20] Natl Naval Med Ctr, Bethesda, MD 20889 USA

[21] Nagoya City Univ, Sch Med, Dept Surg 2, Nagoya, Aichi 4678601, Japan

[22] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet & Radiat Oncol, Chapel Hill, NC 27599 USA

[23] Vall Hebron Univ Hosp, Res Inst, Vall Hebron Inst Oncol, Med Oncol Program, Barcelona 08035, Spain

[24] Autonomous Univ Barcelona, E-08035 Barcelona, Spain

[25] Princess Margaret Hosp, Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2M9, Canada

[26] Princess Margaret Hosp, Univ Hlth Network, Div Appl Mol Oncol, Toronto, ON M5G 2M9, Canada

[27] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada

[28] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA

[29] Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA

[30] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

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

[32] Univ Penn, Dept Med, GI Div, Philadelphia, PA 19104 USA

[33] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

[34] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[35] Univ Michigan, Dept Surg, Thorac Surg Sect, Ann Arbor, MI 48109 USA

[36] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA

[37] Jikei Univ, Sch Med, Dept Obstet & Gynecol, Minato Ku, Tokyo 1058461, Japan

[38] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

NATURE | 2010年 / 463卷 / 7283期

基金：

美国国家卫生研究院;

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; LUNG-CANCER; CHROMOSOMAL BREAKPOINT; MALIGNANT-MELANOMA; ADAPTER PROTEINS; ARRAY CGH; GENES; GENOME; AMPLIFICATION;

D O I：

10.1038/nature08822

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappa B pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.

引用

页码：899 / 905

页数：7

共 49 条

[1] Gene amplification in cancer [J].

Albertson, Donna G. .

TRENDS IN GENETICS, 2006, 22 (08) :447-455

[2] Mutations of the BIK gene in human peripheral B-cell lymphomas [J].

Arena, V ;

Martini, M ;

Luongo, M ;

Capelli, A ;

Larocca, LM .

GENES CHROMOSOMES & CANCER, 2003, 38 (01) :91-96

[3] CLONING THE CHROMOSOMAL BREAKPOINT OF T(14-18) HUMAN LYMPHOMAS - CLUSTERING AROUND JH ON CHROMOSOME-14 AND NEAR A TRANSCRIPTIONAL UNIT ON 18 [J].

BAKHSHI, A ;

JENSEN, JP ;

GOLDMAN, P ;

WRIGHT, JJ ;

MCBRIDE, OW ;

EPSTEIN, AL ;

KORSMEYER, SJ .

CELL, 1985, 41 (03) :899-906

[4] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[5] Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data [J].

Baudis, Michael .

BMC CANCER, 2007, 7 (1)

[6] Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma [J].

Beroukhim, Rameen ;

Getz, Gad ;

Nghiemphu, Leia ;

Barretina, Jordi ;

Hsueh, Teli ;

Linhart, David ;

Vivanco, Igor ;

Lee, Jeffrey C. ;

Huang, Julie H. ;

Alexander, Sethu ;

Du, Jinyan ;

Kau, Tweeny ;

Thomas, Roman K. ;

Shah, Kinial ;

Soto, Horacio ;

Perner, Sven ;

Prensner, John ;

Debiasi, Ralph M. ;

Demichelis, Francesca ;

Hatton, Charlie ;

Rubin, Mark A. ;

Garraway, Levi A. ;

Nelson, Stan F. ;

Liau, Linda ;

Mischel, Paul S. ;

Cloughesy, Tim F. ;

Meyerson, Matthew ;

Golub, Todd A. ;

Lander, Eric S. ;

Mellinghoff, Ingo K. ;

Sellers, William R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (50) :20007-20012

[7] MYC-induced myeloid leukemogenesis is accelerated by all six members of the antiapoptotic BCL family [J].

Beverly, L. J. ;

Varmus, H. E. .

ONCOGENE, 2009, 28 (09) :1274-1279

[8] Integrative genomic approaches identify IKBKE as a breast cancer oncogene [J].

Boehm, Jesse S. ;

Zhao, Jean J. ;

Yao, Jun ;

Kim, So Young ;

Firestein, Ron ;

Dunn, Ian F. ;

Sjostrom, Sarah K. ;

Garraway, Levi A. ;

Weremowicz, Stanislawa ;

Richardson, Andrea L. ;

Greulich, Heidi ;

Stewart, Carly J. ;

Mulvey, Laura A. ;

Shen, Rhine R. ;

Ambrogio, Lauren ;

Hirozane-Kishikawa, Tomoko ;

Hill, David E. ;

Vidal, Marc ;

Meyerson, Matthew ;

Grenier, Jennifer K. ;

Hinkle, Greg ;

Root, David E. ;

Roberts, Thomas M. ;

Lander, Eric S. ;

Polyak, Kornelia ;

Hahn, William C. .

CELL, 2007, 129 (06) :1065-1079

[9] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[10] An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors [J].

Chitale, D. ;

Gong, Y. ;

Taylor, B. S. ;

Broderick, S. ;

Brennan, C. ;

Somwar, R. ;

Golas, B. ;

Wang, L. ;

Motoi, N. ;

Szoke, J. ;

Reinersman, J. M. ;

Major, J. ;

Sander, C. ;

Seshan, V. E. ;

Zakowski, M. F. ;

Rusch, V. ;

Pao, W. ;

Gerald, W. ;

Ladanyi, M. .

ONCOGENE, 2009, 28 (31) :2773-2783

← 1 2 3 4 5 →