Ferber M J, Montoya D P, Yu C, Aderca I, McGee A, Thorland E C, Nagorney D M, Gostout B S, Burgart L J, Boix L, Bruix J, McMahon B J, Cheung T H, Chung T K H, Wong Y F, Smith D I, Roberts L R
Division of Experimental Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Oncogene. 2003 Jun 12;22(24):3813-20. doi: 10.1038/sj.onc.1206528.
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.
慢性感染乙肝病毒（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都是DNA病毒，在侵袭性肿瘤中几乎总是整合到宿主基因组中。病毒整合位点遍布整个基因组，因此推测不存在优先整合位点。已证明许多病毒整合发生在重要的癌症相关基因附近。在对HBV诱导的HCC和HPV诱导的CC的研究中，我们已确定有两个HBV和三个HPV整合到人端粒酶逆转录酶（hTERT）基因中。对这些整合的详细表征显示，四次整合发生在hTERT启动子和上游区域内，第五次整合发生在hTERT基因的第3内含子中。所有整合均未改变hTERT编码序列，且都导致病毒增强子在hTERT附近并列，有可能激活hTERT表达。我们的工作支持这样一种假说，即致癌病毒整合位点并非随机，且病毒整合位点处的基因可能在致癌过程中发挥重要作用。
