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

被引:102
作者
Chan, ATC
Tao, Q
Robertson, KD
Flinn, IW
Mann, RB
Klencke, B
Kwan, WH
Leung, TWT
Johnson, PJ
Ambinder, RF
机构
[1] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA
[2] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Clin Oncol, Shatin, Hong Kong, Peoples R China
[3] Canc Epigenet Tumor Virol Lab, Singapore, Singapore
[4] NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bethesda, MD 20892 USA
[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
关键词
D O I
10.1200/JCO.2004.04.185
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页码:1373 / 1381
页数:9
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