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.
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.
Authors: Weihua Tang; Paula Harmon; Margaret L Gulley; Charles Mwansambo; Peter N Kazembe; Francis Martinson; Clifford Wokocha; Shannon C Kenney; Irving Hoffman; Carlie Sigel; Susan Maygarden; Mariah Hoffman; Carol Shores Journal: Clin Cancer Res Date: 2010-03-16 Impact factor: 12.531
Authors: Jianqing Lin; Jill Gilbert; Michelle A Rudek; James A Zwiebel; Steve Gore; Anchalee Jiemjit; Ming Zhao; Sharyn D Baker; Richard F Ambinder; James G Herman; Ross C Donehower; Michael A Carducci Journal: Clin Cancer Res Date: 2009-09-29 Impact factor: 12.531
Authors: Tanner Dalton; Ekaterina Doubrovina; Dmitry Pankov; Raymond Reynolds; Hanna Scholze; Annamalai Selvakumar; Teresa Vizconde; Bhumesh Savalia; Vadim Dyomin; Christoph Weigel; Christopher C Oakes; Alicia Alonso; Olivier Elemento; Heng Pan; Jude M Phillip; Richard J O'Reilly; Benjamin E Gewurz; Ethel Cesarman; Lisa Giulino-Roth Journal: Blood Date: 2020-05-21 Impact factor: 22.113