Epstein-Barr virus and gastric carcinoma--viral carcinogenesis through epigenetic mechanisms.
Epstein-Barr virus and gastric carcinoma--viral carcinogenesis through epigenetic mechanisms.
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DOI：
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发表时间：
2008
影响因子：
1.4
通讯作者：
H. Uozaki;M. Fukayama
中科院分区：
文献类型：
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作者：
H. Uozaki;M. Fukayama
eb病毒（EBV）相关胃癌（GC）是EBV感染的上皮细胞的单克隆生长，最近才被发现。EBV相关的GC分布在世界各地，估计每年有超过90,000名患者与EBV相关（占总GC的10%）。从组织学特征上看，ebv相关性胃癌可分为淋巴上皮瘤样胃癌和普通型胃癌两种。两者都具有明显的临床病理特征，如易发生多发性癌和残胃癌。虽然ebv潜伏基因在感染细胞中的表达仅限于几个（潜伏期I），但ebv相关GC显示胃细胞表型，对凋亡的抵抗以及免疫调节分子的产生。近年来，许多癌症相关基因的启动子区域的CpG岛甲基化已经被证明是全局的和非随机的，它们的表达降低，如p16 INK4A， p73和E-cadherin。这种异常伴随着EBV基因组本身的甲基化，提示在肿瘤细胞的发育过程中存在病毒驱动的超甲基化过程。需要进一步的研究来确定eb病毒感染、甲基化、转化和胃粘膜优势克隆的精确序列。未来的研究目标和治疗策略也值得期待，例如启动病毒复制或逆转细胞基因的DNA甲基化。
Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) is the monoclonal growth of EBV-infected epithelial cells, and the entity was recognized only recently. EBV-associated GC is distributed worldwide and more than 90,000 patients are estimated to develop GC annually in association with EBV (10% of total GC). EBV-associated GC occurs in two forms in terms of the histological features, i.e., lymphoepithelioma-like GC and ordinary type of GC. Both share characteristic clinicopathological features, such as the preferential occurrence as multiple cancer and remnant stomach cancer. While the expression of EBV-latent genes is restricted to several in the infected cells (Latency I), EBV-associated GC shows gastric cell phenotype, resistance to apoptosis, and the production of immunomodulator molecules. Recently, global and non-random CpG island methylation of the promoter region of many cancer-related genes has been demonstrated with their decreased expression, such as p16 INK4A, p73 and E-cadherin. This abnormality is accompanied by methylation of the EBV genome itself, suggesting a process of virus-driven hypermethylation in the development of neoplastic cells. Further studies are necessary to determine the precise sequence of EBV infection, methylation, transformation and selection of the predominant clone within the stomach mucosa. Future studies are also desirable for the target and strategy of therapy, such as initiating viral replication or reversing the DNA methylation of cellular genes.