Pathogenesis of EB virus-associated neoplasms

EB病毒相关性胃癌：对一株EB病毒相关性胃癌的全球m-RNA表达分析表明，与EB病毒阴性株相比，白细胞介素1-β(IL-1-β)在细胞因子相关基因中高表达。采用原位杂交技术，对EB病毒相关性胃癌手术切除癌组织中IL-1-β基因信号进行了特异性观察。接下来，我们评估了日本胃癌患者中IL-1-β基因的多态性。在EB病毒阴性的胃癌中，某些基因多态性是高危基因，而在EB病毒阳性的胃癌中则不是。因此，IL-1-β可能与EB病毒相关性胃癌的维持有直接关系，也可能通过其基因多态性与EB病毒阴性胃癌的发生发展有关。结果表明，EB病毒相关性胃癌具有全局性和非随机性，随着相应启动子甲基化，癌组织中p16和E-cadherin的免疫组织化学表达降低或异常。用亚硫酸氢盐测序法检测p14启动子的甲基化情况时，29个CpG位点均出现高密度甲基化，而EB病毒阴性的胃癌组织中低密度甲基化和罕见甲基化。由于DNMT1、3a和3b在有无EB病毒感染的胃癌中的表达没有差异，可能存在EB病毒感染胃上皮细胞的特异性机制。脓胸相关淋巴瘤：脓胸相关淋巴瘤表现为EB病毒感染的潜伏期III，类似于艾滋病淋巴瘤。对两种潜伏期III型淋巴瘤的DNA芯片分析表明，有5个基因是脓胸相关淋巴瘤特有的基因，即PRAD、CEB1、GFOD、INSR(胰岛素受体X02160)、MGC23980(C9orf72)。

EB virus-associated gastric carcinoma : Global m-RNA expression analysis of a strain of EB-virus associated gastric carcinoma, which is transplantable in SCID mice, has demonstrated that interleukin 1-β(IL1-β) was highly expressed among the cytokine-related genes, when compared to EB virus-negative strains. IL1-β mRNA signals were specifically observed by in situ hyridization in surgically resected cancer tissues of EB virus-associated gastric carcinoma. Next, IL1-β polymorphisms were evaluated in Japanese patients with gastric cancer. Certain polymorphism was at high risk for EB virus-negative gastric carcinoma, but not for EB virus-positive one. Thus, IL1-β may be directly associated with the maintenance of EB virus-associated gastric carcinoma, and it may be also related with the development of EB virus-negative gastric carcinoma through its polymorphism.Promoter methylation of various cancer-related genes was evaluated by methylation specific PCR. As a result, EB virus-associated gastric carcinoma showed global and non-random, and immunohistochemical expression of p16 and E-cadherin in cancer tissues was decreased or abnormal along with methylation of each corresponding promoter. When the methylation profile of p14 promoter was evaluated by the Bisulfite sequencing, high density methylation was observed in all of 29 CpG sites in contrast to low density and infrequent methylation in EB virus-negative gastric carcinoma. Since expression of DNMT1, 3a and 3b was not different between gastric carcinomas with or without infection of EB virus, there might be a mechanism specific to EB virus infection of stomach epithelial cells.Pyotherax associated lymphoma : Pyothorax-associated lymphoma shows Latency III of EB virus infection similar to AIDS lymphomas. The DNA chip analysis of both Latency III type lymphomas demonstrated that five genes were characteristic to pyothorax-associated lymphoma, that is, PRAD,CEB1,GFOD,INSR (insulin receptor, X02160), MGC23980 (C9orf72).