Study: JGAS00000000015




TitleDNA methylation at HBV integrants and flanking host genomes
AbstractIntegration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either the human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis.
Study Type
Study TypeTumor vs. Matched-Normal


TitleSequence analysis at HBV integrants and flanking host genomes
AgencyGrants-in-Aid for Scientific Research (JSPS KAKEN)
Grant ID23590964


Publication 1
PubMed ID2034275
Publication Statuspublished
Publication 2
PubMed ID8138251
Publication Statuspublished
Publication 3
PubMed ID8666388
Publication Statuspublished

Study Link

URL Link

Study Attribute

NBDC Numberhum0011
Registration date2015-01-13
Submitting organizationSt.Marianna University, School of Medicine
Accession Title Dataset type Data objects Policy
JGAD00000000015 Sequence analysis at HBV integrants and flanking host genomes Amplicon sequencing 10 JGAP00000000001