1996
DOI: 10.1128/jvi.70.3.2000-2007.1996
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Loss and acquisition of duck hepatitis B virus integrations in lineages of LMH-D2 chicken hepatoma cells

Abstract: Hepatocellular carcinoma is the culmination of a series of genetic events which progressively alter the phenotype of a hepatocyte toward malignancy. Hepadnaviral DNA integrations are agents of genetic change which can promote the process of hepatocarcinogenesis. We previously characterized episomally derived duck hepatitis B virus (DHBV) integrations in LMH-D2 cells that replicate wild-type DHBV. In an effort to understand how integrations function as agents of progressive genetic change, we have studied integ… Show more

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Cited by 27 publications
(19 citation statements)
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“…1A). Our previous studies 19,30 have shown that we can detect a viral DNA integration as a distinct band on a Southern blot if it is present in one tenth of the cells in the colony. Thus, our estimates of the numbers of new viral DNA integrations, based on Southern blot data, reflect the stable HBV DNA integrations that occur in the first 3 to 4 cell divisions of any given subclone (that is within the 16-cell stage of the colony).…”
Section: Analysis Of De Novo Hbv Dna Integrations In Untreated Hepg 2mentioning
confidence: 92%
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“…1A). Our previous studies 19,30 have shown that we can detect a viral DNA integration as a distinct band on a Southern blot if it is present in one tenth of the cells in the colony. Thus, our estimates of the numbers of new viral DNA integrations, based on Southern blot data, reflect the stable HBV DNA integrations that occur in the first 3 to 4 cell divisions of any given subclone (that is within the 16-cell stage of the colony).…”
Section: Analysis Of De Novo Hbv Dna Integrations In Untreated Hepg 2mentioning
confidence: 92%
“…1,17,18 Studies on the natural history of integrations of duck hepatitis B virus (DHBV) have directly shown that hepadnavirus integrations can act as hit-and-run mutagens. 19 In one case, a DHBV DNA integration was observed to excise from chromosomal DNA and carry along with it a sizeable piece of host DNA. This type of deletion mechanism could be a driving force for the loss of tumor suppressor genes in infected hepatocytes.…”
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confidence: 99%
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“…Interestingly, molecular analysis of the integrations has shown that virtually all of them contain viral genomes with deletions and rearrangements. Thus, the integration process has been viewed as a pathway in which viral DNA normally destined for CCC DNA formation is diverted into nonfunctional integrations (8,9,20,23). The presence of these integrations can have oncogenic consequences for the host since the integrations contain enhancers which can activate cellular promoter which are normally silent (5)(6)(7).…”
mentioning
confidence: 99%
“…In the case of HBV, a commonly activated protooncogene has not yet been identified in human HCCs. However, the presence of many HBV DNA integrations at sites of chromosomal DNA deletions (23) and translocations (13) have implicated them as general mutagenic agents (8,22).…”
mentioning
confidence: 99%