Hypermethylation of the tumor suppressor gene PRDM1/Blimp-1 supports a pathogenetic role in EBV-positive Burkitt lymphom

T. Zhang, J. Ma, K. Nie, J. Yan, Y. Liu, C. E. Bacchi, E. M. Queiroga, G. Gualco, J. T. Sample, A. Orazi, D. M. Knowles, W. Tam

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

PRDM1/Blimp-1 is a tumor suppressor gene in the activated B-cell subtype of diffuse large B-cell lymphomas. Its inactivation contributes to pathogenesis in this setting by impairing terminal B-cell differentiation induced by constitutive nuclear factor-KB activation. The role of PRDM1 in Burkitt lymphoma (BL) lymphomagenesis is not known. Here we identified hypermethylation of the promoter region and exon 1 of PRDM1 in all six Epstein-Barr virus (EBV)-positive BL cell lines and 12 of 23 (52%) primary EBVpositive BL or BL-related cases examined, but in none of the EBV-negative BL cell lines or primary tumors that we assessed, implying a tumor suppressor role for PRDM1 specifically in EBV-associated BL. A direct induction of PRDM1 hypermethylation by EBV is unlikely, as PRDM1 hypermethylation was not observed in EBV-immortalized B lymphoblastoid cell lines. Treatment of EBV-positive BL cells with 5' azacytidine resulted in PRDM1 induction associated with PRDM1 demethylation, consistent with transcriptional silencing of PRDM1 as a result of DNA methylation. Overexpression of PRDM1 in EBV-positive BL cell lines resulted in cell cycle arrest. Our results expand the spectrum of lymphoid malignancies in which PRDM1 may have a tumor suppressor role and identify an epigenetic event that likely contributes to the pathogenesis of BL.

Original languageEnglish (US)
Article numbere261
JournalBlood Cancer Journal
Volume4
Issue number11
DOIs
StatePublished - Jan 1 2014

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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