Chromosomal translocation and inverted duplication associated with integrated hepatitis B virus in hepatocellular carcinomas

Tokino, Takashi; Fukushige, Shinichi; Nakamura, Toshio; Nagaya, Tsutomu; Murotsu, Tomoaki; Shiga, Kiyoto; Aoki, Naoto; Matsubara, Kazuo

doi:10.1128/jvi.61.12.3848-3854.1987

Cited by 110 publications

(38 citation statements)

References 18 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In HCC from patients with HBsAg, the HBV genome is inserted randomly into the human genome, and may be important in hepatocarcinogenesis. 8,10 The role of HBV in this process in subjects infected with HCV has been controversial. Hepatitis B-related genes were rarely detected by slot-blot analysis of resected liver cancer from patients NOTE.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence of a direct transforming effect of HBV has been reported, with chromosomal deletions and translations at the site of HBV integration and insertion mutagenesis caused by such integration. [8][9][10][11] In addition, HBx protein, encoded by integrated HBV, may be involved in liver cell transformation. HBx protein transforms cultured cells 12,13 and transgenic mice.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in japanese patients with hepatitis C virus

et al. 1999

View full text Add to dashboard Cite

Serological research suggests that hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with the development of hepatocellular carcinoma (HCC). It is unclear how genes of hepatitis viruses participate in hepatocarcinogenesis in patients infected with HCV. We investigated the expression of hepatitis virus-related RNAs in resected liver from 51 patients with HCV antibodies (Ab) and without hepatitis B surface antigen (HBsAg). mRNA transcripts of the genes HBx, HBc, HBs, nonstructural (NS) region 3 of HCV, the 5'-untranslated region (UTR) of HCV, and the 5'-UTR of hepatitis G virus (HGV) were amplified by reverse-transcription polymerase chain reaction (RT-PCR) with specific primers for each gene. The HBx transcript was detected in 19 (37%) tumors and in 8 (16%) specimens of noncancerous tissues (P =.014). The NS3 gene of HCV was detected in 35 (69%) tumors and 41 (80%) noncancerous tissues. HGV RNA was detected in 3 tumors (6%). Patients with HBx transcripts were younger than patients without HBx transcripts (P =.012). HBx transcripts were detected in 3 (33%) of 9 well-differentiated HCCs, in 8 (31%) of 26 moderately differentiated HCCs, and in 8 (50%) of 16 poorly differentiated HCCs. Codon 130 (AAG) and codon 131 (GTC) of HBx were changed to ATG and ATC, respectively, in all HCCs with HBx transcripts. In conclusion, we found that the HBx gene was expressed in many HCCs; the gene might promote hepatocarcinogenesis in patients with HCVAb and without HBsAg, but HGV is not closely related to hepatocarcinogenesis in such patients.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in japanese patients with hepatitis C virus

et al. 1999

View full text Add to dashboard Cite

show abstract

“…c-rnyc), possibly by integrated WHV sequences, has been described (31), but no common integration site of the viral genome has been found. Chromosomal translocations, such as those seen in Epstein-Barr virus-associated Burkitt's lymphomas, which probably lead to oncogene activation, have been reported in some cases of HBV-associated liver tumors (8,15,16). And finally, fusion proteins between the core-and the pol-reading frame similar to those of retroviruses have been found in HBV-associated human tumors by Will et al (32), who speculated that in the absence of viral core particles in the tumor tissues a nonencapsulated, enzymatically active reverse transcriptase probably causes uncontrolled reverse transcription of cellular genes.…”

Section: Although the Role Of Chronic Hepadnavirus Infection In Tumormentioning

confidence: 99%

“…Integrated hepadnavirus DNA is very frequently incomplete and rearranged (10,11,13,34), and a deletion in the C gene region has often been observed (20,21,35,36), a possible result of a site-specific integration of the viral DNA at the direct repeats (16,17,37,38), which are located 5' of the C gene open reading frame. Transcription and expression of viral genes from integrated hepadnavirus DNA may also play a role in tumorigenesis.…”

Section: Although the Role Of Chronic Hepadnavirus Infection In Tumormentioning

confidence: 99%

“…Chronic WHV infection in woodchucks is frequently associated with hepatocellular carcinoma (HCC) (2-6), so this animal is a good model for studying the relationship between chronic hepadnavirus infection and HCC development. Whereas replication of hepadnaviruses (7-9) and integration of viral DNA in tumor cells has been studied extensively (10)(11)(12)(13)(14)(15)(16)(17)(18)(19), transcription of WHV and HBV DNA in tumor tissue has received less attention. Moroy et al (20,21) studied transcription of WHV DNA in chronically infected liver and found two major transcripts of 3.7 and 2.1 kilobases (kb) length; in three tumors they found transcripts of different size.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of woodchuck hepatitis virus DNA and RNA in the hepatocellular carcinomas of woodchucks

et al. 1989

View full text Add to dashboard Cite

Integration and transcription of woodchuck hepatitis virus DNA were studied by Southern and Northern blot analysis in 26 hepatocellular carcinomas and in adjacent nontumor tissue of woodchucks (Marmota monax). All liver tissue chronically infected with woodchuck hepatitis virus contained various amounts of episomal and replicative forms of woodchuck hepatitis virus DNA: episomal and replicative forms of woodchuck hepatitis virus DNA without integration were found in six tumors, episomal and integrated woodchuck hepatitis virus DNA was observed in 18 tumors and exclusively integrated woodchuck hepatitis virus DNA was found in two tumors. In most tumors and in all of the liver tissues chronically infected with woodchuck hepatitis virus, two major woodchuck hepatitis virus RNA species (3.7 and 2.1 kilobases) were detected. In tumors of two other animals (HW76 and HW89) with integrated woodchuck hepatitis virus DNA, only single major transcripts of 3.5 and 2.5 kilobases, respectively, were detected. Hybridization with subcloned woodchuck hepatitis virus DNA probes showed that both aberrant transcripts lacked the C gene and a part of the pre-S1 gene; characterization of corresponding integrated woodchuck hepatitis virus DNA sequences revealed that the C gene was deleted in one tumor, although not in the other. In agreement with the nucleic acid data, we found expression of core protein by Western blotting only in chronically infected liver tissue of these animals, but not in the corresponding tumors. Deletion of the C gene in mRNA may be due to deletion of this gene in the integrated sequences or due to transcriptional regulation.

show abstract

Hepatitis B virus in hepatocarcinogenesis

Feitelson

1999

J. Cell. Physiol.

100

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is an important etiologic agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Although the mechanism whereby HBV causes HCC is not fully understood, it is likely that there are many relevant molecular pathways that contribute to the development of HBV-associated HCC. This review provides an overview of some of these proposed pathways and their relative importance. It also raises questions on basic and translational research that will signficantly contribute to the better understanding of underlying mechanisms, prevention, and treatment of this tumor type.

show abstract

Chromosomal translocation and inverted duplication associated with integrated hepatitis B virus in hepatocellular carcinomas

Cited by 110 publications

References 18 publications

Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in japanese patients with hepatitis C virus

Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in japanese patients with hepatitis C virus

Characterization of woodchuck hepatitis virus DNA and RNA in the hepatocellular carcinomas of woodchucks

Hepatitis B virus in hepatocarcinogenesis

Contact Info

Product

Resources

About