Back to Search
Start Over
Hit-and-run mechanism of HBV-mediated progression to hepatocellular carcinoma.
- Source :
-
Tumori [Tumori] 2005 May-Jun; Vol. 91 (3), pp. 241-7. - Publication Year :
- 2005
-
Abstract
- Aim and Background: Hepatitis B virus is implicated in the development of hepatocellular caracinoma. No oncogenes have been identified within the viral genome. Furthermore, it frequently fragments after integration into the hepatocyte genome. Simultaneous investigations of hepatitis B virus integration patterns and genetic changes in precancerous tissues are important to understand the role played by hepatitis B virus integration in hepatocellular caracinoma.<br />Method: We used a combination approach of dual characterization of highly polymorphic loci and the change in hepatitis B virus-DNA integration pattern. Large regenerative nodules were dissected from 6 explanted hepatitis B virus infected cirrhotic livers. Nodules within each liver segment were schematically mapped and histopathologically analyzed. Genomic DNA from each nodule was analyzed for hepatitis B virus integration and the genetic stability of 12 microsatellite loci including D3S2321, D8S1022, D17S1159, D4S2281, D5S1/2, D16S675, D16S685, D16S490, D16S526, D16S673, D16S677 and D16S690.<br />Results: Data from different liver segments revealed few viral integrations and average allele loss. The most exciting results came from a segment containing a set of clonally and spatially related nodules having similar histologic features, a progressive lineage of allele loss, HBV integration and loss of integration.<br />Conclusions: This model portrait, a scenario of genetic events that precede tumor formation where the acquisition and loss of hepatitis B virus integrations in clonally related regenerative nodules, might explain how the virus acts as a hit-and-run mutagen.
- Subjects :
- Carcinoma, Hepatocellular etiology
DNA, Viral analysis
DNA, Viral genetics
Humans
Liver Neoplasms etiology
Loss of Heterozygosity
Microsatellite Repeats
Mutagenesis
Polymorphism, Genetic
Tumor Cells, Cultured
Carcinoma, Hepatocellular physiopathology
Carcinoma, Hepatocellular virology
Cell Transformation, Neoplastic
Hepatitis B complications
Hepatitis B virus pathogenicity
Liver Neoplasms physiopathology
Liver Neoplasms virology
Virus Integration
Subjects
Details
- Language :
- English
- ISSN :
- 0300-8916
- Volume :
- 91
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Tumori
- Publication Type :
- Academic Journal
- Accession number :
- 16206648
- Full Text :
- https://doi.org/10.1177/030089160509100306