Tao Q, Robertson K D, Manns A, Hildesheim A, Ambinder R F
Oncology Center, Johns Hopkins Medical Institutions, Baltimore, MD, and the National Institutes of Health, Rockville, MD, USA.
Blood. 1998 Feb 15;91(4):1373-81.
Many aspects of Epstein-Barr virus (EBV) and tumor biology have been studied in Burkitt's lymphoma (BL)-derived cell lines. However, in tissue culture, patterns of gene expression and CpG [corrected] methylation often change and viral strain selection may occur. In this report, 10 cases of snap-frozen endemic BL tumors are characterized in terms of viral gene expression, promoter usage, methylation, and viral strain. EBNA1 and BamHI-A rightward transcripts (BART) were detected in 7 of 7 and LMP2A transcripts in 5 of 7 tumors with well-preserved RNA. Transcripts for the other EBNAs and for LMP1 were not detected in any tumor. These tumors differ from BL cell lines in that they lack a variety of lytic cycle transcripts. This pattern of viral gene expression in endemic BL is similar to that reported in peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive individuals. EBNA1 transcripts originated from the Q promoter (Qp) but not C, W, or F promoters that drive transcription of EBNA1 in other circumstances. Whereas Cp has been previously shown to be entirely CpG methylated in BL, bisulfite genomic sequencing showed virtually no methylation in Qp. Type-A EBV was detected in 6 of 10 and type B in 4 of 10 cases. A previously reported 30bp deletion variant in the carboxyl terminal of LMP1 gene was detected in 5 of 10 cases. The association with both A and B strains contrasts with EBV-associated Hodgkin's disease, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease, which are much more consistently associated with A strain virus.
爱泼斯坦-巴尔病毒（EBV）与肿瘤生物学的许多方面已在伯基特淋巴瘤（BL）衍生的细胞系中得到研究。然而，在组织培养中，基因表达模式和CpG[已修正]甲基化常常发生变化，并且可能出现病毒株选择。在本报告中，对10例速冻的地方性BL肿瘤在病毒基因表达、启动子使用、甲基化和病毒株方面进行了特征分析。在7例RNA保存完好的肿瘤中，7例检测到EBNA1和BamHI-A右向转录本（BART），5例检测到LMP2A转录本。在任何肿瘤中均未检测到其他EBNA和LMP1的转录本。这些肿瘤与BL细胞系不同，因为它们缺乏多种裂解周期转录本。地方性BL中的这种病毒基因表达模式与健康EBV血清阳性个体外周血单个核细胞（PBMC）中报道的模式相似。EBNA1转录本源自Q启动子（Qp），而非在其他情况下驱动EBNA1转录的C、W或F启动子。虽然先前已证明Cp在BL中完全被CpG甲基化，但亚硫酸氢盐基因组测序显示Qp中几乎没有甲基化。10例中有6例检测到A型EBV，4例检测到B型。在10例中有五例检测到先前报道的LMP1基因羧基末端30bp缺失变体。与A和B两种毒株的关联与EBV相关的霍奇金淋巴瘤（HL）、鼻咽癌（NPC）和移植后淋巴细胞增殖性疾病（PTLD）形成对比，后者与A型毒株病毒的关联更为一致。
