title: Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatitis B virus (HBV) DNA integration in the host genome is a major mechanism responsible for the etiopathogenetic role exerted by HBV in hepatocellular carcinoma (HCC) development. Extensive analyses evaluating viral integration in HBV surface antigen (HBsAg) negative patients with occult HBV infection (OBI) have not yet been performed. The aim of this study was to investigate and characterize HBV DNA integration in HCC tissues from OBI patients.
  
  
  METHODS
  Tumour DNA extracts from 69 HCC patients (49 HBsAg-negative with occult infection diagnosed by HBV DNA detection in tumour tissues; 10 HBsAg-positive and 10 HBsAg-negative/OBI-negative as control groups) were examined by Alu-PCR technique to reveal HBV DNA integration into the host genome. The molecular characterization of the virus-genome junctions was performed by cloning and sequencing analyses.
  
  
  RESULTS
  Integrated HBV DNA was detected in 37/49 (75.5%) OBI-positive HCC samples, in 8/10 (80%) HBsAg-positive and in 0/10 OBI-negative HCC samples. Nine of 37 (24.3%) integrated viral sequences from OBI-positive cases were inside human genome coding regions and in the remaining cases the localization at intergenic level was frequently adjacent to coding genes. Concerning viral integrants in OBI cases, X gene sequences were found in 14 cases, preS/S sequences in 13, Core sequences in 7, and Polymerase gene sequences in three cases.
  
  
  CONCLUSIONS
  In analogy to what occurs in HBsAg-positive cases, HBV DNA integration is highly prevalent in OBI-related HCCs, it mainly involves X and preS/S viral genomic regions and it frequently occurs at the level of regulatory and functional genes.
authors: Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy.
authors: Carlo
authors: C
authors: Saitta
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Gianluca
authors: G
authors: Tripodi
authors: Division of Oncological Surgery, Department of General Surgery, Oncology and Pathology, University Hospital of Messina, Messina, Italy.
authors: Adalberto
authors: A
authors: Barbera
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Antonio
authors: A
authors: Bertuccio
authors: Gastroenterology and Hepatology Division, University of Torino, San Giovanni Battista Hospital, Torino, Italy.
authors: Antonina
authors: A
authors: Smedile
authors: Gastroenterology and Hepatology Division, University of Torino, San Giovanni Battista Hospital, Torino, Italy.
authors: Alessia
authors: A
authors: Ciancio
authors: Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy.
authors: Giuseppina
authors: G
authors: Raffa
authors: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, "AM & A Migliavacca" Center for the Study of Liver Disease, Milano, Italy.
authors: Angelo
authors: A
authors: Sangiovanni
authors: Division of Oncological Surgery, Department of General Surgery, Oncology and Pathology, University Hospital of Messina, Messina, Italy.
authors: Giuseppe
authors: G
authors: Navarra
authors: Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy.|Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Giovanni
authors: G
authors: Raimondo
authors: Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy.|Department of Pediatric, Gynecologic, Microbiologic and Biomedical Sciences, University of Messina, Messina, Italy.
authors: Teresa
authors: T
authors: Pollicino
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D016679:Genome, Viral; D006509:Hepatitis B / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: Alu-PCR; HBV DNA; HBsAg-negative; HCC; viral integrants