1999 Fiscal Year Final Research Report Summary
Structural and functional alterations of alpha satellite DNA in human hepatocellular carcinoma
| Project/Area Number |
10670458
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
OGATA Norio Toyama Medical and Pharmaceutical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70204063)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Hepatitis B virus / Hepatocellular carcinoma / Alpha satellite DNA |
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| Research Abstract |
Molecular mechanisms of the development of human hepatocellular carcinoma have not been elucidated. We previously found that genomic DNA of hepatitis B virus (HBV) was integrated into alpha satellite DNA located in the centromeric region of chromosomes in human hepatocellular carcinoma cells. We also found that the primary structure of the alpha satellite DNA underwent rearrangement associated with the HBV DNA integration. Because such DNA alterations were not identified in hepatocytes, we considered that the rearrangement of the alpha satellite DNA might have been involved in the development of hepatocellular carcinoma. We analyzed in detail the primary structure of the rearranged alpha satellite DNA. The results showed that the DNA underwent an inverted duplication associated with the HBV integration. To examine possible functions of the rearranged alpha satellite DNA for the development of hepatocellular carcinoma, we tested cell-transforming activity of the cloned, rearranged alpha
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satellite DNA (pYSC) using human diploid cell lines. Up to the present, we have failed in having convincing evidence that the rearranged alpha satellite DNA has the cell-transforming activity.
One goal of antiviral treatment against chronic hepatitis B is to prevent the development of hepatocellular carcinoma. It has been known that HBV genomes are integrated into chromosomes of hepatocytes in chronic hepatitis B. To investigate whether genotypic mutations of HBV would occur during antiviral treatment, whether integration of such mutant viruses may be integrated into hepatocytes, and whether integration of such variant viruses may differ from that of wild-type HBV for the contribution to the development of hepatocellular carcinoma, we examined the occurrence of genotypic mutations of HBV while on lamivudine treatment. The results demonstrated that the mutations occurred in some of patients. Currently, we are examining the integration of such mutant HBV in the liver tissue obtained through needle biopsy. Less
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