Virological characteristics of cervical cancers carrying pure episomal form of HPV16 genome
Virological characteristics of cervical cancers carrying pure episomal form of HPV16 genome
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DOI：
10.1016/j.ygyno.2013.08.026
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发表时间：
2013-11-01
影响因子：
4.7
通讯作者：
Chan, Paul K. S.
中科院分区：
文献类型：
--
作者：
Cheung, Jo L. K.;Cheung, Tak-Hong;Chan, Paul K. S.
目标。许多关于整合的研究报告了关于HPV整合在宫颈癌中的作用的相互矛盾的结果。我们假设，高病毒载量和与HPV整合相关的E2基因中断并不是导致癌症发生的唯一途径。本研究分析了HPV16的病毒载量和整合状态，检测了HPV16 E6/E7的mRNA转录水平，描绘了HPV16的E2和LCR序列变异，并确定了两个E2结合位点的甲基化状态。结果表明，病毒载量与HPV基因组的物理状态无关。在含有纯病毒基因组的浸润性宫颈癌中，3种E6/E7基因的转录水平与含有整合病毒基因组的宫颈癌相似，提示含有病毒基因组的肿瘤也是由E6/E7基因表达上调所介导的，更重要的是，它不依赖于E2基因的整合和破坏。在含有上体病毒基因组的浸润性癌症中上调E6和E7表达的另一种机制可能是位于HPV16启动子区域的两个E2结合位点甲基化的结果。这些观察结果与HPV整合不是导致宫颈癌发生的唯一机制的假设是一致的。(C)2013 Elsevier Inc.保留所有权利。
Objective. Many studies on integration have reported conflicting results regarding the role of HPV integration in cervical cancer. We hypothesized that high viral load and disruption of E2 gene associated with integration of HPV were not the only pathway leading to cancer development.Methods. This study analysed the viral load and integration status of HPV16, measured the HPV16 E6/E7 mRNA transcript levels, delineated the E2 and LCR sequence variation, and determined the methylation status of two E2 binding sites.Results. The results showed that viral load was not associated with the physical status of HPV genome. Levels of the three E6/E7 mRNA transcripts in invasive cervical cancers containing purely episomal viral genome were found to be similar to those containing integrated viral genome, suggesting that cancers containing episomal viral genome were also mediated by an up-regulated E6/E7 mRNA expression, and more importantly, did not depend on integration and disruption of the E2 gene.Conclusions. The alternative mechanism that up-regulated the expression of E6 and E7 in invasive cancers harbouring episomal viral genome was likely to be a consequence of methylation of the two E2 binding sites located at the promoter region of HPV16. These observations are in line with the hypothesis that HPV integration was not the only mechanism leading to the development of cervical cancer. (C) 2013 Elsevier Inc. All rights reserved.