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

被引:1
作者
Bruni, R [1 ]
Argentini, C [1 ]
DUgo, E [1 ]
Giuseppetti, R [1 ]
Rapicetta, M [1 ]
机构
[1] IST SUPER SANITA, VIROL LAB, I-00161 ROME, ITALY
关键词
D O I
10.1007/s007050050096
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:499 / 509
页数:11
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