Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 22, Issue 8, Pages 1373-1381Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2004.04.185
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Funding
- NCI NIH HHS [U01 CA 70062, P01 CA 15396] Funding Source: Medline
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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.
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