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Extensive analysis of duplicated-inverted hepatitis B virus integrations in human hepatocellular carcinoma

Authors
 Pascal Pineau  ;  Agne' s Marchio  ;  Marie-Genevie' ve Mattei  ;  Won-Ho Kim  ;  Jung-Koo Youn  ;  Pierre Tiollais  ;  Anne Dejean 
Citation
 JOURNAL OF GENERAL VIROLOGY, Vol.79(3) : 591-600, 1998 
Journal Title
 JOURNAL OF GENERAL VIROLOGY 
ISSN
 0022-1317 
Issue Date
1998
MeSH
Adult ; Carcinoma, Hepatocellular/virology* ; Chromosomes, Human, Pair 10 ; Chromosomes, Human, Pair 8 ; DNA, Viral/analysis ; Gene Expression Regulation ; Hepatitis B virus/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Molecular Sequence Data ; Recombination, Genetic ; Tumor Cells, Cultured ; Virus Integration*
Abstract
Hepatitis B virus (HBV) DNA is found chromosomally integrated into the genome of the majority of hepatocellular carcinomas (HCC) arising in chronic HBV carriers suggesting that, in some instances, viral sequences may be directly responsible for oncogenic conversion. In an attempt to clarify the oncogenic potential of integrated HBV sequences, we performed an extensive analysis of two single integrations present in HCC which developed in non-cirrhotic livers from HBsAg-positive Korean patients. In both cases, integrated viral sequences were characterized by a duplicated-inverted configuration involving the flanking cellular sequences, a pattern consistently found in many amplicons isolated from mammalian cells. Integration sites are characterized by an AT-rich content and the presence of topoisomerase I and II cleavage target sequences as well as other recombination-prone motifs. The chromosomal locations of the integration sites were determined as 8q13 and 10q22 in the human genome, two regions known to harbour genes involved in tumorigenesis. The cis-activating potential of the integrations in their original configuration was also investigated in a transient transfection assay in HepG2 cells. Integrated sequences, rather than activating heterologous promoters, show either no activity or a weak tendency to inhibit activation of neighbouring reporter genes. The implications of our findings for the understanding of primary liver cancer development are discussed.
Full Text
https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-79-3-591#tab2
DOI
10.1099/0022-1317-79-3-591
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/176716
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