Woodchuck hepatitis virus DNA integration in a common chromosomal region of the woodchuck genome in two independent hepatocellular carcinomas

Woodchuck hepatitis virus DNA integration in a common chromosomal region of the woodchuck genome... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Woodchuck hepatitis virus DNA integration in a common chromosomal region of the woodchuck genome in two independent hepatocellular carcinomas

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Publisher
Springer Journals
Copyright
Copyright © Wien by 1997 Springer-Verlag/
Subject
Legacy
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s007050050096
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Archives of VirologySpringer Journals

Published: Mar 1, 1997

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