Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers
Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers
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DOI：
10.1038/sj.onc.1206528
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发表时间：
2003-06-12
期刊：
影响因子：
8
通讯作者：
Roberts, LR
中科院分区：
文献类型：
--
作者：
Ferber, MJ;Montoya, DP;Roberts, LR
慢性感染B型肝炎病毒（HBV）和高危型人乳头瘤病毒（HPV）分别是肝细胞癌（HCC）和宫颈癌（CC）的重要危险因素。HBV和HPV是DNA病毒，在侵袭性肿瘤中几乎总是整合到宿主基因组中。病毒整合位点出现在整个基因组中，导致假定没有优选的整合位点。许多病毒整合已被证明发生在重要的癌症相关基因附近。在HBV诱导的HCC和HPV诱导的CC的研究中，我们已经确定了两种HBV和三种HPV整合到人端粒酶逆转录酶（hTERT）基因中。对整合的详细表征显示，四个整合发生在hTERT启动子和上游区域内，第五个整合发生在hTERT基因的内含子3中。这些整合都没有改变hTERT编码序列，并且都导致病毒增强子在hTERT附近并置，从而潜在地激活hTERT表达。我们的工作支持这一假设，即致癌病毒整合的网站是非随机的，在病毒整合的网站上的基因可能在致癌作用中发挥重要作用。
Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.