Woodchuck hepatitis virus DNA integration in a common chromosomal region of the woodchuck genome in two independent hepatocellular carcinomas.
In woodchuck hepatocellular carcinoma (HCC) the myc-oncogene family (particularly N-myc2) and the win locus of cellular genome have been reported as frequent targets for integration of woodchuck hepatitis virus (WHV) DNA. In this paper a further cellular locus, b3n, is reported as recurrent target for WHV integration in woodchuck HCC. Cloning and sequencing of a WHV-DNA integration and its cellular flanking regions showed that viral DNA was inserted in a chromosomal region already described for WHV integration in another single HCC. The two integration sites are only 0.5 kb apart. A link between WHV integration in b3n and HCC development may be postulated. Careful analysis of the sequence of the unoccupied locus revealed that, in addition to Alu-like repeats and a gag-like coding region, already described, several features of Matrix Attachment Region (MAR) sequences are present. Thus (part of) b3n might be a previously unrecognized MAR. Organization of the chromatin in functional domains and regulation of gene expression are some functions attributed to MAR sequences. The occurrence of WHV-DNA integration close to the same putative MAR in two different HCCs suggests that a mechanism of deregulation of MAR functions by WHV insertion might act in some liver tumors.
Bruni
R
R
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Argentini
C
C
D'Ugo
E
E
Giuseppetti
R
R
Rapicetta
M
M
D000818:Animals; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology*; D002874:Chromosome Mapping; D004273:DNA, Neoplasm; D004279:DNA, Viral; D005260:Female; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D008392:Marmota; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D016662:Virus Integration
D004273:DNA, Neoplasm; D004279:DNA, Viral