title: Sequencing of human-viral DNA junctions in hepatocellular carcinoma from patients with HCV and occult HBV infection.
abstract: DNA of free hepatitis B viruses (HBV) has been detected in the liver of patients infected with hepatitis C virus (HCV). It is unknown whether HBV DNA is integrated into such livers; if so, it may affect hepatocarcinogenesis. Hepatocellular carcinomas (HCCs) from 34 patients without HBV surface antigen (HBsAg) and with anti-HCV, and from 7 patients with HBsAg and without anti-HCV as controls, were examined, using the cassette-ligation-mediated polymerase chain reaction and primers based on HBV DNA sequence. In the controls, HBV DNA had been integrated into human DNA of all HCCs. On the basis of HBV DNA in tumor tissue, 23 of the 34 patients with anti-HCV had occult infection. Junctions between human DNA and HBV DNA were detected in 10 of the 34 patients without HBsAg and with anti-HCV. HBV DNA was integrated into chromosome 11q in 4 of the 10 HCCs with junctions. The DNA to either side of the human-viral junctions was sequenced. Clinically, the mean tumor size of these 10 HCCs was 39 mm; that of the 24 HCCs without integrated HBV was 25 mm. The surrounding tissue was cirrhotic in 2 of the 10 former HCCs and in 16 of the latter 24 HCCs. In conclusion, integrated HBV was detected in some patients with HCV infection; in these patients, the integrated DNA was associated with accelerated hepatocarcinogenesis.
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.forename: Shoji
authors.initials: S
authors.lastname: Kubo
authors.forename: Masaru
authors.initials: M
authors.lastname: Enomoto
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Koh
authors.forename: Tadashi
authors.initials: T
authors.lastname: Takeda
authors.forename: Susumu
authors.initials: S
authors.lastname: Shiomi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hirohashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Shuzo
authors.initials: S
authors.lastname: Otani
mesh_terms: D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004247:DNA / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D016662:Virus Integration
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D004247:DNA