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Integration of hepatitis B virus containing mutations in the core promoter/X gene in patients with hepatocellular carcinoma
- Source :
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 35(11)
- Publication Year :
- 2003
-
Abstract
- Integration of hepatitis B virus is thought to be an essential step in hepatitis B virus associated hepatocarcinogenesis. Mutations at nucleotides 1762 and 1764 in the hepatitis B virus, within a sequence encoding both the core promoter gene and the X gene, have been found frequently in patients with hepatocellular carcinoma. However, integration of these mutant sequences has not been reported to date. Methods. A 228-base pair segment of the hepatitis B virus core promoter gene was amplified from hepatocellular carcinomas and adjacent non-tumourous liver tissue by nested PCR and sequenced. Integration of hepatitis B virus into human genomic DNA was investigated using the ‘genome walking’ method. Results. Point mutations were found in both hepatitis B virus nucleotides 1762 and 1764 in 8 of 14 hepatocellular carcinoma tissues (57%) and in 11 of 14 adjacent non-tumourous liver tissues (79%). Three patients were evaluated using the ‘genome walking’ method; all were found to have hepatitis B virus DNA integrated in their hepatocellular carcinoma (two patients) and/or in their non-tumourous liver tissue (three patients). Integration occurred in all tissues near host genomic sites that are prone to integration. Hepatitis B virus was integrated at or near the hepatitis B virus DR1 site in all samples, and all contained truncated X gene sequences that have been reported to be capable of producing fusion transcripts with transactivation potential. Conclusions. Integrated hepatitis B virus DNA containing core promoter mutations at nucleotides 1762 and 1764 was found in hepatocellular carcinoma and/or adjacent non-tumourous liver tissue of three patients. These findings leave open the possibility that insertional mutagenesis or transactivation by fusion transcripts resulting from hepatitis B virus integration could play a role in hepatocarcinogenesis in some patients.
- Subjects :
- Male
Hepatitis B virus
Carcinoma, Hepatocellular
Hepatitis B virus DNA polymerase
Virus Integration
Viral transformation
Biology
medicine.disease_cause
Hepatitis B virus PRE beta
Insertional mutagenesis
medicine
MiR-122
Humans
Point Mutation
Promoter Regions, Genetic
Aged
Mutation
Hepatology
Base Sequence
Viral Core Proteins
Liver Neoplasms
Gastroenterology
Sequence Analysis, DNA
Middle Aged
medicine.disease
Virology
Hepatocellular carcinoma
Case-Control Studies
DNA, Viral
Female
Subjects
Details
- ISSN :
- 15908658
- Volume :
- 35
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
- Accession number :
- edsair.doi.dedup.....5e9b31f21144ed3310d5336a170e92c6