Cooperative Epigenetic Modulation by Cancer Amplicon Genes

Lixin Rui, N. C.Tolga Emre, Michael J. Kruhlak, Hye Jung Chung, Christian Steidl, Graham Slack, George W. Wright, Georg Lenz, Vu N. Ngo, Arthur L. Shaffer, Weihong Xu, Hong Zhao, Yandan Yang, Laurence Lamy, R. Eric Davis, Wenming Xiao, John Powell, David Maloney, Craig J. Thomas, Peter MöllerAndreas Rosenwald, German Ott, Hans Konrad Muller-Hermelink, Kerry Savage, Joseph M. Connors, Lisa M. Rimsza, Elias Campo, Elaine S. Jaffe, Jan Delabie, Erlend B. Smeland, Dennis D. Weisenburger, Wing C. Chan, Randy D. Gascoyne, David Levens, Louis M. Staudt

Research output: Contribution to journalArticle

204 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)590-605
Number of pages16
JournalCancer cell
Volume18
Issue number6
DOIs
StatePublished - Dec 14 2010

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Rui, L., Emre, N. C. T., Kruhlak, M. J., Chung, H. J., Steidl, C., Slack, G., Wright, G. W., Lenz, G., Ngo, V. N., Shaffer, A. L., Xu, W., Zhao, H., Yang, Y., Lamy, L., Davis, R. E., Xiao, W., Powell, J., Maloney, D., Thomas, C. J., ... Staudt, L. M. (2010). Cooperative Epigenetic Modulation by Cancer Amplicon Genes. Cancer cell, 18(6), 590-605. https://doi.org/10.1016/j.ccr.2010.11.013