Integration of hepatitis virus DNA near c-myc in woodchuck hepatocellular carcinoma.
A total of 33 hepatocellular carcinomas, induced in woodchucks by chronic infection with woodchuck hepatitis virus (WHV), a virus closely related to the human hepatitis B virus, were analyzed for the state of viral DNA, the expression of viral genes and of different cellular proto-oncogenes. Low levels of viral replication and presence of integrated viral forms including sequences of the enhancer element, appeared as a general rule in these tumors. Enhanced expression of one or more of the nuclear protooncogenes: c-myc, N-myc, c-fos, c-jun and jun-B was frequently observed. In two hepatomas, elevated expression and allelic alterations of c-myc were subsequent to integration of WHV DNA near the c-myc coding domain. The viral strategy for insertional activation of c-myc in these tumors appeared basically identical to that of mammalian retroviruses in T-cell lymphomas of mice and rats. Whether insertional mutagenesis of different oncogenes may be more generally linked to liver oncogenesis induced by WHV and hepatitis B viruses remains to be determined.
Hsu
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TY
Unité de Recombinaison et Expression Génétique (INSERM U.163, Institut Pasteur, Paris, France.
Fourel
G
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Etiemble
J
J
Tiollais
P
P
Buendia
M A
MA
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000662:veterinary; D004279:DNA, Viral / Q000235:genetics*; D015870:Gene Expression; D016259:Genes, myc; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000662:veterinary; D008242:Lysogeny / Q000235:genetics; D008392:Marmota; D012367:RNA, Viral / Q000235:genetics; D015183:Restriction Mapping
D004279:DNA, Viral; D012367:RNA, Viral