Epigenetic alterations in nasopharyngeal carcinoma and Epstein-Barr virus (EBV) associated gastric carcinoma: a lesson in contrasts

Hans-Helmut Niller, Ferenc Banati, Janos Minarovits

Abstract


Epstein-Barr virus (EBV) is associated with diverse hematological and epithelial malignancies, such as Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and others. Upon infection of B‑lymphoid and epithelial cells, the virus adopts distinct gene expression patterns which depend on the cellular epigenetic machinery. Moreover, virus infection regularly induces modifications of the viral and host cell transcriptomes and epigenomes through the interaction of viral proteins with cellular epigenetic regulators. Viral latent and immediate early proteins may principally contribute to the reprogramming of the cellular epigenome. While EBV-immortalized B lymphoblastoid cell lines are characterized by a massive hypomethylation of the cellular genome and genome-wide reorganization and loss of heterochromatic histone marks, EBV associated malignancies are characterized by local hypermethylation of CpG islands (CGI) at specific gene sets characteristic for each tumor type. Groups of hypermethylated promoters may represent unique EBV associated epigenetic signatures in EBV-associated gastric carcinomas (EBVaGC) and nasopharyngeal carcinomas (NPC). Here, we review the similarities and differences between EBVaGC and NPC with an emphasis on the epigenetic perspective. Both tumors exhibit a CpG island methylator phenotype (CIMP) and a very high load of hypermethylated tumor suppressor genes, EBVaGC more so than the EBV-negative GC subtypes. However, according to present knowledge, there is only a very small set of hypermethylated gene loci which EBVaGC and NPC have in common. Construction of whole genome comparative methylomes and genome-wide analysis of further epigenetic marks may illuminate the patho-epigenetics of these EBV-associated carcinomas.


Keywords


Chromosomal band, CpG island, Epigenetic field, Hit and run oncogenesis, Hypermethylation, Latency, Lytic cycle, Methylator phenotype, Methylome, Nitrosamines, Oncoprotein, Pioneer transcription factor, Tumor promoter, Tumor suppressor

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References


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DOI: http://dx.doi.org/10.15383/JNPC.9

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