Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells / 癌症
Chinese Journal of Cancer
;
(12): 604-608, 2014.
Artigo
em Inglês
| WPRIM
| ID: wpr-349632
ABSTRACT
Epstein-Barr virus (EBV) is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma (NPC) and approximately 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 (genome-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 methylation accumulation, indicating that EBV acts as a direct epigenetic driver for these cancers. Mechanistically, oncogenic modulation of cellular CpG methylation machinery, such as DNA methyltransferases (DNMTs), by EBV-encoded viral proteins accounts for the EBV-induced high CpG methylation 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Neoplasias Gástricas
/
Proteínas Virais
/
Carcinoma
/
Neoplasias Nasofaríngeas
/
Regiões Promotoras Genéticas
/
Herpesvirus Humano 4
/
Ilhas de CpG
/
Metilação de DNA
/
Infecções por Vírus Epstein-Barr
/
Células Epiteliais
Limite:
Humanos
Idioma:
Inglês
Revista:
Chinese Journal of Cancer
Ano de publicação:
2014
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS