title: Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues.
abstract: Hepatitis B virus (HBV) is a hepatotropic virus causing hepatitis, cirrhosis and hepatocellular carcinoma (HCC). The methylation status of the HBV DNA in its different forms can potentially provide insight into the pathogenesis of HBV-related liver diseases, including HCC, however this is unclear. The goal of this study is to obtain comprehensive DNA methylation profiles of the three putative CpG islands in the HBV DNA in infected livers, with respect to liver disease progression. The extent of methylation in these CpG islands was first assessed using bisulfite PCR sequencing with a small set of tissue samples, followed by analysis using both quantitative bisulfite-specific PCR and quantitative methylation-specific PCR assays in a larger sample size (n = 116). The level of HBV CpG island 3 methylation significantly correlated with hepatocarcinogenesis. We also obtained, for the first time, evidence of rare, non-CpG methylation in CpG island 2 of the HBV genome in infected liver. Comparing methylation of the HBV genome to three known HCC-associated host genes, APC, GSTP1, and RASSF1A, we did not identify a significant correlation between these two groups.
authors.affiliation: JBS Science, Inc., Doylestown, Pennsylvania.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan, Republic of China.
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.affiliation: JBS Science, Inc., Doylestown, Pennsylvania.
authors.forename: Sitong
authors.initials: S
authors.lastname: Chen
authors.affiliation: JBS Science, Inc., Doylestown, Pennsylvania.
authors.forename: Batbold
authors.initials: B
authors.lastname: Boldbaatar
authors.affiliation: JBS Science, Inc., Doylestown, Pennsylvania.
authors.forename: Adam
authors.initials: A
authors.lastname: Clemens
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Selena Y
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ran
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan, Republic of China.
authors.forename: Chi-Tan
authors.initials: CT
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Haitao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Block
authors.affiliation: JBS Science, Inc., Doylestown, Pennsylvania.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ying-Hsiu
authors.initials: YH
authors.lastname: Su
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D004279:DNA, Viral / Q000032:analysis* / Q000378:metabolism; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology*; D008107:Liver Diseases / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D004279:DNA, Viral; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi