Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

D. W. Dawson, J. S. Hong, R. R. Shen, S. W. French, J. J. Troke, Y. Z. Wu, S. S. Chen, Dorina Gui, M. Regelson, Y. Marahrens, H. C. Morse, J. Said, C. Plass, M. A. Teitell

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread.

Original languageEnglish (US)
Pages (from-to)4243-4252
Number of pages10
JournalOncogene
Volume26
Issue number29
DOIs
StatePublished - Jun 21 2007

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Keywords

  • B-cell lymphoma
  • DNA methylation
  • TCL1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Dawson, D. W., Hong, J. S., Shen, R. R., French, S. W., Troke, J. J., Wu, Y. Z., Chen, S. S., Gui, D., Regelson, M., Marahrens, Y., Morse, H. C., Said, J., Plass, C., & Teitell, M. A. (2007). Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas. Oncogene, 26(29), 4243-4252. https://doi.org/10.1038/sj.onc.1210211