Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene

被引:229
作者
Paterlini-Bréchot, P [1 ]
Saigo, K
Murakami, Y
Chami, M
Gozuacik, D
Mugnier, C
Lagorce, D
Bréchot, C
机构
[1] Hop Necker Enfants Malad, INSERM, Pasteur Unit 370, Fac Med Necker, F-75015 Paris, France
[2] Chiba Univ, Dept Surg 2, Sch Med, Chiba 2608670, Japan
[3] Hop Necker Enfants Malad, Dept Biostat & Med Informat, F-75015 Paris, France
关键词
Hepatitis B Virus; insertional mutagenesis; hepatocellular carcinoma; hTERT;
D O I
10.1038/sj.onc.1206492
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
Integration of Hepatitis B Virus (HBV) DNA into liver cell DNA has been well established, but its implication in liver carcinogenesis is still being debated. In particular, insertion of the viral genome into cellular genes has been viewed as a rare event. By using HBV-Alu PCR, we have now isolated, from nine hepatocellular carcinomas, nine HBV-DNA integration sites showing that the viral genome mutates key regulatory cellular genes: neurotropic tyrosin receptor kinase 2 (NTRK2) gene, IL-1R-associated kinase 2 (IRAK2) gene, p42 mitogen-activated protein kinase 1 (p42MAPK1) gene, inositol 1,4,5-triphosphate receptor type 2 (IP3R2) gene, inositol 1,4,5-triphosphate receptor (IP3R) type 1 (IP3R1) gene, alpha 2,3 sialyltransferase (ST3GAL VI or SITA) gene, thyroid hormone uncoupling protein (TRUP) gene, EMX2-like gene, and human telomerase reverse transcriptase (hTERT) gene. This result brings to 15 the total number of genes targeted by HBV in a study of 22 human liver cancers. Overall, we found that both the inositol 1,4,5-triphosphate receptor gene and the telomerase gene were targeted by HBV in two different tumors. Thus, HBV frequently targets cellular genes involved in cell signalling and some of them may be preferential targets of the viral integration.
引用
收藏
页码:3911 / 3916
页数:6
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