In woodchuck hepatocellular carcinoma (HCC) the myc -oncogene family (particularly N- myc 2) 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.
Archives of Virology – Springer Journals
Published: Mar 1, 1997
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