Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers

被引:159
作者
Ferber, MJ
Montoya, DP
Yu, C
Aderca, I
McGee, A
Thorland, EC
Nagorney, DM
Gostout, BS
Burgart, LJ
Boix, L
Bruix, J
McMahon, BJ
Cheung, TH
Chung, TKH
Wong, YF
Smith, DI
Roberts, LR [1 ]
机构
[1] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
[3] Mayo Clin, Div Expt Pathol, Rochester, MN 55905 USA
[4] Mayo Clin, Div Gastroenterol & Gen Surg, Rochester, MN 55905 USA
[5] Mayo Clin, Dept Obstet & Gynaecol, Rochester, MN 55905 USA
[6] Mayo Clin, Div Anat Pathol, Rochester, MN 55905 USA
[7] Univ Barcelona, IMD Hosp Clin, BCLC Grp Liver Unit, Barcelona 08036, Spain
[8] Alaska Native Med Ctr, Anchorage, AK 99508 USA
[9] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynaecol, Hong Kong, Hong Kong, Peoples R China
关键词
hepatitis B virus; human papillomavirus; telomerase reverse transcriptase; hepatocellular carcinoma; cervical cancer; viral integration;
D O I
10.1038/sj.onc.1206528
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3813 / 3820
页数:8
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