The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset

被引：414

作者：

Ceol, Craig J. ^{[1
]}

Houvras, Yariv ^{[1
,2
]}

Jane-Valbuena, Judit ^{[3
,4
,5
]}

Bilodeau, Steve ^{[6
]}

Orlando, David A. ^{[6
]}

Battisti, Valentine ^{[7
]}

Fritsch, Lauriane ^{[7
]}

Lin, William M. ^{[3
,4
,5
]}

Hollmann, Travis J. ^{[8
]}

Ferre, Fabrizio ^{[9
]}

Bourque, Caitlin ^{[1
]}

Burke, Christopher J. ^{[1
]}

Turner, Laura ^{[1
]}

Uong, Audrey ^{[1
]}

Johnson, Laura A. ^{[3
,4
,5
]}

Beroukhim, Rameen ^{[3
,4
,5
]}

Mermel, Craig H. ^{[3
,4
,5
]}

Loda, Massimo ^{[8
]}

Ait-Si-Ali, Slimane ^{[7
]}

Garraway, Levi A. ^{[3
,4
,5
]}

Young, Richard A. ^{[6
]}

Zon, Leonard I. ^{[1
]}

机构：

[1] Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA

[3] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA

[4] Harvard Univ, Ctr Canc Genome Discovery, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA

[5] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA

[6] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[7] Univ Paris Diderot, Epigenet & Destin Cellulaire UMR7216, CNRS, F-75013 Paris, France

[8] Harvard Univ, Ctr Mol Oncol Pathol, Brigham & Womens Hosp, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA

[9] Univ Roma La Sapienza, A Rossi Fanelli Biochem Sci Dept, I-00185 Rome, Italy

来源：

NATURE | 2011年 / 471卷 / 7339期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

MALIGNANT-MELANOMA; BRAF MUTATIONS; HUMAN CANCER; GENES; NEVI; SENESCENCE; EXPRESSION; REPRESSION; LYSINE-9; CELLS;

D O I：

10.1038/nature09806

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：

The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway(1,2). BRAF(V600E) mutations are also present in benign melanocytic naevi(3), highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes(4,5). For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis.

引用

页码：513 / +

页数：6

共 23 条

[1] 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

[2] The landscape of somatic copy-number alteration across human cancers [J].

Beroukhim, Rameen ;

Mermel, Craig H. ;

Porter, Dale ;

Wei, Guo ;

Raychaudhuri, Soumya ;

Donovan, Jerry ;

Barretina, Jordi ;

Boehm, Jesse S. ;

Dobson, Jennifer ;

Urashima, Mitsuyoshi ;

Mc Henry, Kevin T. ;

Pinchback, Reid M. ;

Ligon, Azra H. ;

Cho, Yoon-Jae ;

Haery, Leila ;

Greulich, Heidi ;

Reich, Michael ;

Winckler, Wendy ;

Lawrence, Michael S. ;

Weir, Barbara A. ;

Tanaka, Kumiko E. ;

Chiang, Derek Y. ;

Bass, Adam J. ;

Loo, Alice ;

Hoffman, Carter ;

Prensner, John ;

Liefeld, Ted ;

Gao, Qing ;

Yecies, Derek ;

Signoretti, Sabina ;

Maher, Elizabeth ;

Kaye, Frederic J. ;

Sasaki, Hidefumi ;

Tepper, Joel E. ;

Fletcher, Jonathan A. ;

Tabernero, Josep ;

Baselga, Jose ;

Tsao, Ming-Sound ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Janne, Pasi A. ;

Daly, Mark J. ;

Nucera, Carmelo ;

Levine, Ross L. ;

Ebert, Benjamin L. ;

Gabriel, Stacey ;

Rustgi, Anil K. ;

Antonescu, Cristina R. ;

Ladanyi, Marc ;

Letai, Anthony .

NATURE, 2010, 463 (7283) :899-905

[3] SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state [J].

Bilodeau, Steve ;

Kagey, Michael H. ;

Frampton, Garrett M. ;

Rahl, Peter B. ;

Young, Richard A. .

GENES & DEVELOPMENT, 2009, 23 (21) :2484-2489

[4] Distinct sets of genetic alterations in melanoma [J].

Curtin, JA ;

Fridlyand, J ;

Kageshita, T ;

Patel, HN ;

Busam, KJ ;

Kutzner, H ;

Cho, KH ;

Aiba, S ;

Bröcker, EB ;

LeBoit, PE ;

Pinkel, D ;

Bastian, BC .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (20) :2135-2147

[5] Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes [J].

Dalgliesh, Gillian L. ;

Furge, Kyle ;

Greenman, Chris ;

Chen, Lina ;

Bignell, Graham ;

Butler, Adam ;

Davies, Helen ;

Edkins, Sarah ;

Hardy, Claire ;

Latimer, Calli ;

Teague, Jon ;

Andrews, Jenny ;

Barthorpe, Syd ;

Beare, Dave ;

Buck, Gemma ;

Campbell, Peter J. ;

Forbes, Simon ;

Jia, Mingming ;

Jones, David ;

Knott, Henry ;

Kok, Chai Yin ;

Lau, King Wai ;

Leroy, Catherine ;

Lin, Meng-Lay ;

McBride, David J. ;

Maddison, Mark ;

Maguire, Simon ;

McLay, Kirsten ;

Menzies, Andrew ;

Mironenko, Tatiana ;

Mulderrig, Lee ;

Mudie, Laura ;

O'Meara, Sarah ;

Pleasance, Erin ;

Rajasingham, Arjunan ;

Shepherd, Rebecca ;

Smith, Raffaella ;

Stebbings, Lucy ;

Stephens, Philip ;

Tang, Gurpreet ;

Tarpey, Patrick S. ;

Turrell, Kelly ;

Dykema, Karl J. ;

Khoo, Sok Kean ;

Petillo, David ;

Wondergem, Bill ;

Anema, John ;

Kahnoski, Richard J. ;

Teh, Bin Tean ;

Stratton, Michael R. .

NATURE, 2010, 463 (7279) :360-363

[6] Mutations of the BRAF gene in human cancer [J].

Davies, H ;

Bignell, GR ;

Cox, C ;

Stephens, P ;

Edkins, S ;

Clegg, S ;

Teague, J ;

Woffendin, H ;

Garnett, MJ ;

Bottomley, W ;

Davis, N ;

Dicks, N ;

Ewing, R ;

Floyd, Y ;

Gray, K ;

Hall, S ;

Hawes, R ;

Hughes, J ;

Kosmidou, V ;

Menzies, A ;

Mould, C ;

Parker, A ;

Stevens, C ;

Watt, S ;

Hooper, S ;

Wilson, R ;

Jayatilake, H ;

Gusterson, BA ;

Cooper, C ;

Shipley, J ;

Hargrave, D ;

Pritchard-Jones, K ;

Maitland, N ;

Chenevix-Trench, G ;

Riggins, GJ ;

Bigner, DD ;

Palmieri, G ;

Cossu, A ;

Flanagan, A ;

Nicholson, A ;

Ho, JWC ;

Leung, SY ;

Yuen, ST ;

Weber, BL ;

Siegler, HF ;

Darrow, TL ;

Paterson, H ;

Marais, R ;

Marshall, CJ ;

Wooster, R .

NATURE, 2002, 417 (6892) :949-954

[7] A BIOMARKER THAT IDENTIFIES SENESCENT HUMAN-CELLS IN CULTURE AND IN AGING SKIN IN-VIVO [J].

DIMRI, GP ;

LEE, XH ;

BASILE, G ;

ACOSTA, M ;

SCOTT, C ;

ROSKELLEY, C ;

MEDRANO, EE ;

LINSKENS, M ;

RUBELJ, I ;

PEREIRASMITH, O ;

PEACOCKE, M ;

CAMPISI, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) :9363-9367

[8] A Subset of the Histone H3 Lysine 9 Methyltransferases Suv39h1, G9a, GLP, and SETDB1 Participate in a Multimeric Complex [J].

Fritsch, Lauriane ;

Robin, Philippe ;

Mathieu, Jacques R. R. ;

Souidi, Mouloud ;

Hinaux, Helene ;

Rougeulle, Claire ;

Harel-Bellan, Annick ;

Ameyar-Zazoua, Maya ;

Ait-Si-Ali, Slimane .

MOLECULAR CELL, 2010, 37 (01) :46-56

[9] Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma [J].

Garraway, LA ;

Widlund, HR ;

Rubin, MA ;

Getz, G ;

Berger, AJ ;

Ramaswamy, S ;

Beroukhim, R ;

Milner, DA ;

Granter, SR ;

Du, JY ;

Lee, C ;

Wagner, SN ;

Li, C ;

Golub, TR ;

Rimm, DL ;

Meyerson, ML ;

Fisher, DE ;

Sellers, WR .

NATURE, 2005, 436 (7047) :117-122

[10] The Tol2kit:: A multisite Gateway-based construction kit for Tol2 transposon transgenesis constructs [J].

Kwan, Kristen M. ;

Fujimoto, Esther ;

Grabher, Clemens ;

Mangum, Benjamin D. ;

Hardy, Melissa E. ;

Campbell, Douglas S. ;

Parant, John M. ;

Yost, H. Joseph ;

Kanki, John P. ;

Chien, Chi-Bin .

DEVELOPMENTAL DYNAMICS, 2007, 236 (11) :3088-3099

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