Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells
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摘要Epstein-Barr virus (EBV) is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma (NPC) and -10% of gastric cancer (GC) worldwide. Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC. However, even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC (EBVaGC), suggesting a predominant role of epigenetic abnormities, especially promoter CpG methylation, in the pathogenesis of NPC and EBVaGC. High frequencies of promoter methylation of tumor suppressor genes (TSGs) have been frequently reported in NPC and EBVaGC, with several EBV-induced methylated TSGs identified. Further characterization of the epigenomes (genonne-wide CpG methylation profile-methylome) of NPC and EBVaGC shows that these EBV-associated tumors display a unique high CpG methylation epigenotype with more extensive gene nnethylation accumulation, indicating that EBV acts as a direct epigenetic driver for these cancers. Mechanistically, oncogenic modulation of cellular CpG methylation machinery, such as DNA nnethyltransferases (DNMTs), by EBV-encoded viral proteins accounts for the EBV-induced high CpG nnethylation epigenotype in NPC and EBVaGC. Thus, uncovering the EBV-associated unique epigenotype of NPC and EBVaGC would provide new insight into the molecular pathogenesis of these unique EBV-associated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.
著者Li LL, Zhang Y, Guo BB, Chan FKL, Tao Q
期刊名稱Chinese Journal of Cancer
出版年份2014
月份12
日期1
卷號33
期次12
出版社BioMed Central
頁次604 - 608
國際標準期刊號1000-467X
電子國際標準期刊號1944-446X
語言英式英語
關鍵詞CpG methylation; DNA methyltransferase; Epstein-Barr virus; gastric cancer; nasopharyngeal carcinoma; tumor suppressor gene
Web of Science 學科類別Oncology

上次更新時間 2020-23-11 於 00:11