Our objective is to study the pathogenic relationship between human hepatitis B virus (HBV) and the development of hepatocellular carcinoma at the molecular level. Our goal is to fill the gap between putative """"""""hepatoma oncogene"""""""" and HBV chronic infection/integration. The major effort will be to examine potential amplification, expression, and transposition of oncogenes and cellular DNA near the HBV integration site.
Specific aims are as follows: 1. To continue and complete our current project of HT14 and FOCUS hepatomas. Both appear to have a single site of HBV integration. This project includes DNA sequencing of both HT14 and FOCUS flanking cellular DNA, isolation of the preintegration site from FOCUS, chromosomal localization of HT14 and FOCUS HBV, expression of FOCUS HBV, etc. 2. To follow up several putative amplification loci near the site of HBV integration in hepatomas R16, HT2, HT12, HT14. 3. To trace the history of potential HBV transposition in PLC/PRF/5 hepatoma cell lines. 4. To look for specific chromosomal abnormality with the strategy of combinations of classic and molecular cytogenetics, RFLP probes will be used in this approach (Restriction Fragment Length Polymorphism). 5. To analyze HBV or oncogene specific RNA in adult or fetal hepatoma.
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