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Abstract 1373: Comprehensive analysis of HBV DNA methylation in liver tissues of hepatitis B, cirrhosis and hepatocellular carcinoma patients
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Abstract 1373: Comprehensive analysis of HBV DNA methylation in liver tissues of hepatitis B, cirrhosis and hepatocellular carcinoma patients

Surbhi Jain, Sitong Chen, Batbold Boldbaatar, Selena Y. Lin, Ran Yan, Chi-Tan Hu, Haitao Guo, Timothy M. Block, Wei song and Ying-Hsiu Su
Cancer research (Chicago, Ill.), v 74(19_Supplement), pp 1373-1373
01 Oct 2014
DOI: https://doi.org/10.1158/1538-7445.AM2014-1373

Abstract

Abstract Hepatitis B virus (HBV) is a hepatotropic virus causing hepatitis, cirrhosis and hepatocellular carcinoma. In patients, HBV DNA circulates in blood as virion DNA and exists in hepatocytes both as nuclear form (episomal cccDNA and integrated DNA) and as cytoplasmic core DNA form. It has been reported that HBV infection up-regulates DNMTs and thus induces epigenetic changes in the host cells. Understanding the methylation status of the HBV DNA in its different forms can potentially provide insight into the pathogenesis of HBV-related liver diseases including hepatocarcinogenesis. Previous studies conducted in patient serum and in cell cultures have demonstrated that the CpG islands of HBV virion DNA are in the unmethylated state, and cccDNA methylation has been extensively studied for its role in the regulation of transcription, but very few studies have investigated the methylation status of integrated HBV DNA in human liver tissues. To better understand the methylation status of HBV DNA in hepatitis B, cirrhosis and HCC, a comprehensive methylation profile of three CpG islands in the HBV genome was assessed by BS-sequencing, and methylation of each of the 3 CpG islands was compared by using bisulfite specific PCR and methylation specific PCR assays in a larger sample size. We observed that the methylation of CpG island 1 and 3 of HBV DNA from liver tissues was significantly higher in HCC as compared to hepatitis and cirrhosis. We also obtained, for the first time, the evidence of rare non-CpG methylation in the CpG island 1 and 2 of HBV genome in liver tissues. The overall co-relation of HBV genome methylation and disease progression was also investigated. In addition, no co-relation between the methylation levels of the HBV genome and host genome was found, suggesting independent mechanisms regulate the methylation of host and viral genomes. The mechanisms of HBV genome methylation in liver disease and its regulation are discussed. Citation Format: Surbhi Jain, Sitong Chen, Batbold Boldbaatar, Selena Y. Lin, Ran Yan, Chi-Tan Hu, Haitao Guo, Timothy M. Block, Wei song, Ying-Hsiu Su. Comprehensive analysis of HBV DNA methylation in liver tissues of hepatitis B, cirrhosis and hepatocellular carcinoma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1373. doi:10.1158/1538-7445.AM2014-1373

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Oncology
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