Characterization of integration patterns and flanking cellular sequences of hepatitis B virus in childhood hepatocellular carcinomas
| Autor: | Tsuey-Ying Hsu, Yen-Hsuan Ni, Daw-Jen Tsuei, Mei-Hwei Chang, Pei-Jer Chen |
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| Rok vydání: | 2002 |
| Předmět: |
Hepatitis B virus
Carcinoma Hepatocellular Molecular Sequence Data medicine.disease_cause Orthohepadnavirus Virology Gene duplication medicine Humans Gene DNA Primers Southern blot Recombination Genetic Base Sequence biology Inverse polymerase chain reaction Liver Neoplasms Gene Amplification biology.organism_classification medicine.disease digestive system diseases Blotting Southern Infectious Diseases Hepadnaviridae Hepatocellular carcinoma DNA Viral |
| Zdroj: | Journal of Medical Virology. 68:513-521 |
| ISSN: | 1096-9071 0146-6615 |
| DOI: | 10.1002/jmv.10240 |
| Popis: | Hepatitis B virus (HBV) DNA integration into host chromosomes is detected in more than 80% of HBV-related hepatocellular carcinomas (HCC), yet its significance in tumor development remains obscure. In this study, we re-examined the integration pattern of HBV in childhood HCC tissues, which has less environmental confounding factors than adult HCC. The HBV junctions and flanking cellular sequences were amplified from five childhood HCC patients by the inverse polymerase chain reaction (IPCR) method using primers located near HBV direct repeats (DR) 1 and 2. The viral junctions in nine of the ten obtained IPCR clones were demonstrated to be located near HBV DR1, and their patterns were classified to type I integrants. Southern blot analyses demonstrate that the cellular junctions derived from two of the five HCC tissues were male specific and contained sequences homologous to human long interspersed DNA elements (LINE-1). HBV integrant of one HCC tissue (1217T) was integrated into a RNA binding motif Y chromosome (RBMY) gene. The expression of RBMY, which is normally found only in male germ cells, was detected in HCC tissue 1217T by RT-PCR but not in the corresponding non-tumor liver tissue. The prevalence of RBMY expression in liver tissues from the tumor and non-tumor parts of ten other HCC children and seven biliary atresia (BA) children was studied by RT-PCR. No RBMY transcripts were detected in the non-tumor parts of HCC patients or the cirrhotic livers of BA children, whereas 30% (three of ten) of HCC tissues specifically expressed RBMY. The results indicate that HBV integration and activation of RBMY gene expression in liver cells may be associated with the development of childhood HCC. |
| Databáze: | OpenAIRE |
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