Accumulation of genetic alterations in a human hepatoma cell line transfected with hepatitis B virus

Livezey, Kristin; Simón, Daniela

doi:10.1016/s0027-5107(97)00068-7

Cited by 18 publications

(7 citation statements)

References 31 publications

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“…Viral integration may destabilise telomeres and other chromosomal regions, making them susceptible to recombination [Rogler et al, 1985;Sandros and Stenman, 1990;Kao et al, 1993;van der Drift et al, 1994;Wilke et al, 1996;Jox et al, 1997;Livezey and Simon, 1997;Lopez-Borges et al, 1998]. The low frequency of nonclonal chromosome aberrations we observed in PHA-stimulated cells may therefore be related to the integrated virus.…”

Section: Discussionmentioning

confidence: 79%

Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3

et al. 1999

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An unusually high level of latent HHV-6 infection has been documented in the peripheral blood and/or bone marrow cells of a small group of patients with predominantly malignant lymphoid disorders, and in at least one healthy individual. We have shown previously in peripheral blood mononuclear cells (PBMCs) of three patients, two with a history of lymphoma and one with multiple sclerosis, a specific target site for latent integration of the full-length HHV-6 viral genome on the distal short arm of chromosome 17, in band p13.3. Fluorescence in situ hybridization (FISH) procedures were used to map more precisely the location of the viral integration site in one of those patients, relative to two known oncogenes mapped previously, namely CRK, and the more telomeric ABR oncogene. It is shown that the HHV-6 integration site is located at least 1,000 kb telomeric of ABR, and is very likely to map close to or within the telomeric sequences of 17p. This finding is significant given that human telomeric-like repeats flank the terminal ends of the HHV-6 genome. Cytogenetic studies showed evidence of karyotype instability in the peripheral blood cells infected latently.

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Section: Discussionmentioning

confidence: 79%

Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3

et al. 1999

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“…Integration of HBV DNA into HepG2 cells or into the host chromosomes of transgenic mice has resulted in chromosomal instability (Hino et al, 1991;Livezey and Simon, 1997), which may contribute to LOH at many sites during chronic infection. In fact, LOH was widespread in tumors derived from HBV carriers compared to HBV negative patients (Laurent-Puig et al, 2001), suggesting that chronic HBV infection is associated with chromosomal instability.…”

Section: Early Events In Hepatocarcinogenesismentioning

confidence: 99%

Genetic mechanisms of hepatocarcinogenesis

et al. 2002

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The development of hepatocellular carcinoma (HCC) is a multistep process associated with changes in host gene expression, some of which correlate with the appearance and progression of tumor. Preneoplastic changes in gene expression result from altered DNA methylation, the actions of hepatitis B and C viruses, and point mutations or loss of heterozygosity (LOH) in selected cellular genes. Tumor progression is characterized by LOH involving tumor suppressor genes on many chromosomes and by gene ampli®cation of selected oncogenes. The changes observed in di erent HCC nodules are often distinct, suggesting heterogeneity on the molecular level. These observations suggest that there are multiple, perhaps redundant negative growth regulatory pathways that protect cells against transformation. An understanding of the molecular pathogenesis of HCC may provide new markers for tumor staging, for assessment of the relative risk of tumor formation, and open new opportunities for therapeutic intervention.

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“…Whether HBV infection and integration of HBV DNA play a role in chromosomal instability is an interesting issue. It has been shown that peripheral blood cells of HBV chronic carriers present a higher incidence of chromosome breaks than matched uninfected populations and that HBV‐transfected hepatoma cells HepG2 have de novo genetic alterations at several chromosomal sites 78,79. Large rearrangements of genomic DNA frequently accompany HBV DNA integration in host chromosomes 80.…”

Section: Genetic Instability In Hepatocellular Carcinomamentioning

confidence: 99%

Genetic Alterations and Oncogenic Pathways in Hepatocellular Carcinoma

Lévy

Renard

et al. 2002

Annals of the New York Academy of Sciences

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Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. Chronic infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) have been implicated in about 80% of cases worldwide, and other known environmental risk factors, including alcohol abuse and dietary intake of aflatoxin B1, might synergize with viral infections. Recent insight into the molecular mechanisms leading to HCC development has been provided by the identification of major genetic abnormalities revealed by genomewide allelotype studies and molecular cytogenetic analysis. Moreover, several oncogenic pathways have been implicated in malignant transformation of liver cells. Inactivation of the p53 tumor suppressor gene by mutations and allelic deletions in about 30% of HCC cases has been associated predominantly with exposure to aflatoxin B1 and HBV infection. By contrast, a mutation in the β‐catenin gene in around 22% of HCCs is more rare in HBV‐associated tumors. Activation of cyclin D1 and disruption of the Rb pathway are also commonly involved in liver tumorigenesis. New major challenges include the identification of candidate genes located in frequently altered chromosomal regions and that of oncogenic pathways driven by different risk factors. This search might shed some light on the tumorigenic role of HBV and HCV. It might also permit accurate evaluation of major targets for prognostic and therapeutic intervention.

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Accumulation of genetic alterations in a human hepatoma cell line transfected with hepatitis B virus

Cited by 18 publications

References 31 publications

Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3

Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3

Genetic mechanisms of hepatocarcinogenesis

Genetic Alterations and Oncogenic Pathways in Hepatocellular Carcinoma

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