title: Role of hepatitis B virus DNA integration in human hepatocarcinogenesis.
abstract: Liver cancer ranks sixth in cancer incidence, and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, which arises from hepatocytes and accounts for approximately 70%-85% of cases. Hepatitis B virus (HBV) frequently causes liver inflammation, hepatic damage and subsequent cirrhosis. Integrated viral DNA is found in 85%-90% of HBV-related HCCs. Its presence in tumors from non-cirrhotic livers of children or young adults further supports the role of viral DNA integration in hepatocarcinogenesis. Integration of subgenomic HBV DNA fragments into different locations within the host DNA is a significant feature of chronic HBV infection. Integration has two potential consequences: (1) the host genome becomes altered ("cis" effect); and (2) the HBV genome becomes altered ("trans" effect). The cis effect includes insertional mutagenesis, which can potentially disrupt host gene function or alter host gene regulation. Tumor progression is frequently associated with rearrangement and partial gain or loss of both viral and host sequences. However, the role of integrated HBV DNA in hepatocarcinogenesis remains controversial. Modern technology has provided a new paradigm to further our understanding of disease mechanisms. This review summarizes the role of HBV DNA integration in human carcinogenesis.
authors.affiliation: Hoang Hai, Akihiro Tamori, Norifumi Kawada, Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan.
authors.forename: Hoang
authors.initials: H
authors.lastname: Hai
authors.affiliation: Hoang Hai, Akihiro Tamori, Norifumi Kawada, Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.affiliation: Hoang Hai, Akihiro Tamori, Norifumi Kawada, Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology*; D016679:Genome, Viral; D055106:Genome-Wide Association Study; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D007249:Inflammation; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D009154:Mutation; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins; D016662:Virus Integration
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: Cis effect; Hepatitis B virus; Hepatocarcinogenesis; Integration; Trans effect; Whole genome sequencing