Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues

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. T...

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Main Authors: Jain, Surbhi, Chang, Ting-Tsung, Chen, Sitong, Boldbaatar, Batbold, Clemens, Adam, Lin, Selena Y., Yan, Ran, Hu, Chi-Tan, Guo, Haitao, Block, Timothy M., Song, Wei, Su, Ying-Hsiu
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650678/
id pubmed-4650678
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spelling pubmed-46506782015-11-24 Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues Jain, Surbhi Chang, Ting-Tsung Chen, Sitong Boldbaatar, Batbold Clemens, Adam Lin, Selena Y. Yan, Ran Hu, Chi-Tan Guo, Haitao Block, Timothy M. Song, Wei Su, Ying-Hsiu Article 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. Nature Publishing Group 2015-05-22 /pmc/articles/PMC4650678/ /pubmed/26000761 http://dx.doi.org/10.1038/srep10478 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Jain, Surbhi
Chang, Ting-Tsung
Chen, Sitong
Boldbaatar, Batbold
Clemens, Adam
Lin, Selena Y.
Yan, Ran
Hu, Chi-Tan
Guo, Haitao
Block, Timothy M.
Song, Wei
Su, Ying-Hsiu
spellingShingle Jain, Surbhi
Chang, Ting-Tsung
Chen, Sitong
Boldbaatar, Batbold
Clemens, Adam
Lin, Selena Y.
Yan, Ran
Hu, Chi-Tan
Guo, Haitao
Block, Timothy M.
Song, Wei
Su, Ying-Hsiu
Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues
author_facet Jain, Surbhi
Chang, Ting-Tsung
Chen, Sitong
Boldbaatar, Batbold
Clemens, Adam
Lin, Selena Y.
Yan, Ran
Hu, Chi-Tan
Guo, Haitao
Block, Timothy M.
Song, Wei
Su, Ying-Hsiu
author_sort Jain, Surbhi
title Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues
title_short Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues
title_full Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues
title_fullStr Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues
title_full_unstemmed Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues
title_sort comprehensive dna methylation analysis of hepatitis b virus genome in infected liver tissues
description 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.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650678/
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