Cooperative Epigenetic Modulation by Cancer Amplicon Genes

被引：212

作者：

Rui, Lixin ^{[1
]}

Emre, N. C. Tolga ^{[1
]}

Kruhlak, Michael J. ^{[2
]}

Chung, Hye-Jung ^{[3
]}

Steidl, Christian ^{[4
]}

Slack, Graham ^{[4
]}

Wright, George W. ^{[5
]}

Lenz, Georg ^{[1
]}

Ngo, Vu N. ^{[1
]}

Shaffer, Arthur L. ^{[1
]}

Xu, Weihong ^{[1
]}

Zhao, Hong ^{[1
]}

Yang, Yandan ^{[1
]}

Lamy, Laurence ^{[1
]}

Davis, R. Eric ^{[1
]}

Xiao, Wenming ^{[6
]}

Powell, John ^{[6
]}

Maloney, David ^{[7
]}

Thomas, Craig J. ^{[7
]}

Moeller, Peter ^{[8
]}

Rosenwald, Andreas ^{[9
]}

Ott, German ^{[10
,11
]}

Muller-Hermelink, Hans Konrad ^{[9
]}

Savage, Kerry ^{[4
]}

Connors, Joseph M. ^{[4
]}

Rimsza, Lisa M. ^{[12
,13
]}

Campo, Elias ^{[14
]}

Jaffe, Elaine S. ^{[3
]}

Delabie, Jan ^{[15
]}

Smeland, Erlend B. ^{[16
,17
]}

Weisenburger, Dennis D. ^{[18
,19
]}

Chan, Wing C. ^{[18
,19
]}

Gascoyne, Randy D. ^{[4
]}

Levens, David ^{[3
]}

Staudt, Louis M. ^{[1
]}

机构：

[1] NCI, Metab Branch, Bethesda, MD 20892 USA

[2] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA

[3] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA

[4] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada

[5] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA

[6] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA

[7] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA

[8] Univ Ulm, Dept Pathol, D-89081 Ulm, Germany

[9] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany

[10] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany

[11] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany

[12] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA

[13] SW Oncol Grp, Ann Arbor, MI 48106 USA

[14] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain

[15] Oslo Univ Hosp, Pathol Clin, N-0027 Oslo, Norway

[16] Oslo Univ Hosp, Inst Canc Res, N-0027 Oslo, Norway

[17] Univ Oslo, Ctr Canc Biomed, N-0316 Oslo, Norway

[18] Univ Nebraska, Dept Pathol, Omaha, NE 68198 USA

[19] Univ Nebraska, Dept Microbiol, Omaha, NE 68198 USA

来源：

CANCER CELL | 2010年 / 18卷 / 06期

基金：

英国医学研究理事会;

关键词：

B-CELL LYMPHOMA; CLASSICAL HODGKIN LYMPHOMA; REED-STERNBERG CELLS; EXON; 12; MUTATIONS; JAK2; INHIBITOR; HISTONE H3; INTERLEUKIN-13; RECEPTOR; LYSINE; AMPLIFICATION; HP1;

D O I：

10.1016/j.ccr.2010.11.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chromosome band 9p24 is frequently amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL). To identify oncogenes in this amplicon, we screened an RNA interference library targeting amplicon genes and thereby identified JAK2 and the histone demethylase JMJD2C as essential genes in these lymphomas. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas by decreasing tyrosine 41 phosphorylation and increasing lysine 9 trimethylation of histone H3, promoting heterochromatin formation. MYC, a major target of JAK2-mediated histone phosphorylation, was silenced after JAK2 and JMJD2C inhibition, with a corresponding increase in repressive chromatin. Hence, JAK2 and JMJD2C cooperatively remodel the PMBL and HL epigenome, offering a mechanistic rationale for the development of JAK2 and JMJD2C inhibitors in these diseases.

引用

页码：590 / 605

页数：16

共 55 条

[1] Kinetic analysis of the interleukin-13 receptor complex [J].

Andrews, AL ;

Holloway, JW ;

Puddicombe, SM ;

Holgate, ST ;

Davies, DE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (48) :46073-46078

[2] Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain [J].

Bannister, AJ ;

Zegerman, P ;

Partridge, JF ;

Miska, EA ;

Thomas, JO ;

Allshire, RC ;

Kouzarides, T .

NATURE, 2001, 410 (6824) :120-124

[3]

Bentz M, 2001, GENE CHROMOSOME CANC, V30, P393, DOI 10.1002/1098-2264(2001)9999:9999<::AID-GCC1105>3.0.CO

[4]

2-I

[5] Oncogenic pathway signatures in human cancers as a guide to targeted therapies [J].

Bild, AH ;

Yao, G ;

Chang, JT ;

Wang, QL ;

Potti, A ;

Chasse, D ;

Joshi, MB ;

Harpole, D ;

Lancaster, JM ;

Berchuck, A ;

Olson, JA ;

Marks, JR ;

Dressman, HK ;

West, M ;

Nevins, JR .

NATURE, 2006, 439 (7074) :353-357

[6] The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 [J].

Cloos, Paul A. C. ;

Christensen, Jesper ;

Agger, Karl ;

Maiolica, Alessio ;

Rappsilber, Juri ;

Antal, Torben ;

Hansen, Klaus H. ;

Helin, Kristian .

NATURE, 2006, 442 (7100) :307-311

[7] VEGFR1-activity-independent metastasis formation [J].

Dawson, Michelle R. ;

Duda, Dan G. ;

Fukumura, Dai ;

Jain, Rakesh K. .

NATURE, 2009, 461 (7262) :E4-E5

[8] Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease [J].

Diehl, V ;

Franklin, J ;

Pfreundschuh, M ;

Lathan, B ;

Paulus, U ;

Hasenclever, D ;

Tesch, H ;

Herrmann, R ;

Dörken, B ;

Müller-Hermelink, H ;

Dühmke, E ;

Loeffler, M .

NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (24) :2386-2395

[9] Comprehensive genomic analysis of desmoplastic medulloblastomas:: identification of novel amplified genes and separate evaluation of the different histological components [J].

Ehrbrecht, A ;

Müller, U ;

Wolter, M ;

Hoischen, A ;

Koch, A ;

Radlwimmer, B ;

Actor, B ;

Mincheva, A ;

Pietsch, T ;

Lichter, P ;

Reifenberger, G ;

Weber, RG .

JOURNAL OF PATHOLOGY, 2006, 208 (04) :554-563

[10] Overexpression of I kappa B alpha without inhibition of NF-κB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells [J].

Emmerich, F ;

Meiser, M ;

Hummel, M ;

Demel, G ;

Foss, HD ;

Jundt, F ;

Mathas, S ;

Krappmann, D ;

Scheidereit, C ;

Stein, H ;

Dorken, B .

BLOOD, 1999, 94 (09) :3129-3134

← 1 2 3 4 5 6 →