Azacitidine induces demethylation of the Epstein-Barr virus genome in tumors

Anthony T.C. Chan, Qian Tao, Keith D. Robertson, Ian W. Flinn, Risa B. Mann, Barbara Klencke, Wing Hong Kwan, Thomas Wai Tong Leung, Philip J. Johnson, Richard F. Ambinder

Research output: Contribution to journalArticle

Abstract

Purpose: To determine whether therapy with a DNA methyltransferase inhibitor is effective in achieving demethylation and gene re-expression in tumor DNA in patients. Methods: Biopsy specimens were obtained from patients with Epstein-Barr virus-associated tumors, enrolled on a clinical trial of 5-azacitidine, within 72 hours of the conclusion of the last infusion of the first cycle of therapy, and compared to pretreatment specimens. Methylation-specific polymerase chain reaction, bisulfite genomic sequencing, and immunohistochemistry were used to assess demethylation and gene re-expression. Results: Substantial degrees of demethylation were detected in all latent and lytic Epstein-Barr virus promoters examined. Immunohistochemistry suggested activation of a previously silent viral antigen expression in one instance. Conclusion: Pharmacologic reversal of dense CpG methylation in tumor tissue can be achieved in patients.

Original languageEnglish (US)
Pages (from-to)1373-1381
Number of pages9
JournalJournal of Clinical Oncology
Volume22
Issue number8
DOIs
StatePublished - 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chan, A. T. C., Tao, Q., Robertson, K. D., Flinn, I. W., Mann, R. B., Klencke, B., Kwan, W. H., Leung, T. W. T., Johnson, P. J., & Ambinder, R. F. (2004). Azacitidine induces demethylation of the Epstein-Barr virus genome in tumors. Journal of Clinical Oncology, 22(8), 1373-1381. https://doi.org/10.1200/JCO.2004.04.185