Multiple rearrangements and activated expression of c-myc induced by woodchuck hepatitis virus integration in a primary liver tumour.
Woodchuck hepatitis virus (WHV) is a small, partially double-stranded DNA virus. Like the related human hepatitis B virus (HBV), WHV induces acute and chronic hepatitis and hepatocellular carcinoma (HCC) in its natural host. WHV DNA integration into c-myc and N-myc, resulting in deregulated expression of these genes, has been described previously in woodchuck HCC. We have analysed a woodchuck liver tumour in which WHV DNA was integrated in the c-myc gene. The virus insertion provoked multiple alterations in one c-myc allele, probably involving secondary deletions and mutations. Integrated viral DNA, including promotor and enhancer sequences, acted as an insertional mutagen, leading to enhanced expression of heterogenous c-myc transcripts ranging from 7.2 to 14 kb in size, strikingly longer than normal 2.3-kb c-myc RNA. These results provide an additional example in which the oncogenic activation of a myc gene by cis-acting effect of WHV insertion may play a critical role in virus-induced woodchuck HCC.
Wei
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Y
Unité de Recombinaison et Expression génétique, INSERM-U.163, Institut Pasteur, Paris.
Ponzetto
A
A
Tiollais
P
P
Buendia
M A
MA
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000382:microbiology / Q000662:veterinary; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D016259:Genes, myc; D015613:Hepadnaviridae / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000662:veterinary; D008392:Marmota / Q000235:genetics*; D011995:Recombination, Genetic; D016662:Virus Integration