Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jul;4(3):150-7.

Hepatitis B virus genome asymmetry in hepatocellular carcinoma

Zahra Shokrgozar  1 , Sirous Tayebi  2 , Zarrin Minucheher  3 , Ashraf Mohamadkhani  2
Affiliations

Hepatitis B virus genome asymmetry in hepatocellular carcinoma

Zahra Shokrgozar et al. Middle East J Dig Dis. 2012 Jul.

Abstract

Background: The association between hepatitis B virus (HBV) mutations and hepatocarcinogenesis were reported in the literature. Preference for G over C in the leading DNA strand has been reported to account for the asymmetry in nucleotide (nt) composition. The aim of this study was to analyze the complete genome sequence and compositional asymmetry of HBV in different stages of hepatitis B.

Methods: Full genome sequencing of 24 patients with chronic hepatitis B, some of whom also had cirrhosis and hepatocellular carcinoma (HCC) was performed. Mutations analysis was implemented in a comparison with a HBV genotype D reference from an international DNA database. CpGProD, a web-based application, was used to evaluate CG content and predict CpG islands.

Results: All strains were 3182 base pairs (bp) in length, except for two cases of HCC in which 9 and 21 nt, respectively, were deleted in preS2. The genetic relatedness of these isolates was 97%-100%. There were common CpG-rich regions in all 24 isolated full genome sequences, however a strong negative GC skew for forming a CpG island in the minus strand were exhibited in overlap with enhancer I in three HCC patients, a cirrhotic patient and three with chronic hepatitis.

Conclusion: The high percentage of sequence identity between HBV isolates in our patients demonstrates that genomic factors, except for genotype, are involved in hepatocarcinogenesis. Variations in GC content which were caused by a different spectrum of mutations may affect DNA compositional asymmetry and epigenetic modification of HBV DNA in HCC.

Keywords: HBV genome CpG; Hepatitis B virus (HBV); Hepatocellular carcinoma (HCC).

PubMed Disclaimer

Figures

Fig 1
Fig 1
Fig 2
Fig 2
See this image and copyright information in PMC

References

    1. Liu S, Zhang H, Gu C, Yin J, He Y, Xie J. et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst. 2009;101:1066–82. - PMC - PubMed
    1. Barone M, Spano D, D’Apolito M, Centra M, Lasalandra C, Capasso M. et al. Gene expression analysis in HBV transgenic mouse liver: a model to study early events related to hepatocarcinogenesis. Mol Med. 2006;12:115–23. - PMC - PubMed
    1. Fattovich G, Brollo L, Giustina G, Noventa F, Pontisso P, Alberti A. et al. Natural history and prognostic factors for chronic hepatitis type B. Gut. 1991;32:294–8. - PMC - PubMed
    1. Mohamadkhani A, Montazeri G, Poustchi H. The Importance of Hepatitis B Virus Genome Diversity in Basal Core Promoter Region. Middle East J Dig Dis. 2011;3:13–9. - PMC - PubMed
    1. Lobry JR. Asymmetric substitution patterns in the two DNA strands of bacteria. Mol Biol Evol. 1996;13:660–5. - PubMed

LinkOut - more resources