Methylation status of the Epstein-Barr virus major latent promoter C in iatrogenic B cell lymphoproliferative disease - Application of PCR-based analysis
Methylation status of the Epstein-Barr virus major latent promoter C in iatrogenic B cell lymphoproliferative disease - Application of PCR-based analysis
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DOI：
10.1016/s0002-9440(10)65157-7
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发表时间：
1999-08-01
影响因子：
6
通讯作者：
Ambinder, RF
中科院分区：
文献类型：
--
作者：
Tao, Q;Swinnen, LJ;Ambinder, RF
EB病毒(Epstein-Barr Virus，EBV)的主要潜在启动子C驱动病毒核蛋白的表达，这些蛋白在淋巴细胞永生化过程中起重要作用，也是细胞毒性T细胞免疫监视的靶标。C启动子的高甲基化使其转录沉默。该启动子甲基化，在伯基特淋巴瘤、霍奇金氏病、鼻咽癌和鼻部淋巴瘤中不表达。然而，在作为EBV相关淋巴增殖性疾病模型的EBV永生化淋巴母细胞系中，它永远不会甲基化。我们使用一种敏感的基于聚合酶链式反应的C启动子甲基化分析方法，分析了医源性EBV相关B细胞淋巴组织增生性疾病，主要是移植后淋巴瘤的C启动子甲基化。我们的结果显示，13名患者中有3名患者的淋巴组织增生性疾病中存在病毒DNA甲基化的异质性。在其中两名患者的样本中，仅检测到甲基化的病毒DNA，并相应地限制了病毒核抗原的表达。C启动子甲基化的异质性和相关转录本的表达可能是淋巴增生性病变生长特性的重要决定因素，并可能为某些肿瘤对停用或减少免疫抑制治疗失败的原因提供解释。
The Epstein-Barr virus (EBV) major latent promoter C drives the expression of viral nuclear proteins important in lymphocyte immortalization and as targets for immune surveillance by cytotoxic T cells. Hypermethylation of the C promoter silences its transcription. This promoter is methylated and silent in Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and nasal lymphoma. However, it is never methylated in the EBV-immortalized lymphoblastoid cell lines that serve as a model for EBV-associated lymphoproliferative disease. We have analyzed C promoter methylation in iatrogenic EBV-associated B-cell lymphoproliferative disease, mainly posttransplant lymphoma, using a sensitive polymerase chain reaction-based C promoter methylation assay. Our results showed heterogeneity in lymphoproliferative disease with methylation of viral DNA in specimens from 3 of 13 patients. In specimens from two of these patients, only methylated viral DNA was detected and viral nuclear antigen expression Tvas correspondingly restricted. Heterogeneity in C promoter methylation and expression of associated transcripts may be an important determinant of the growth properties of lymphoproliferative lesions and may provide an explanation for the failure of some tumors to respond to withdrawal or reduction of immunosuppressive therapy.