Pre-S2 deletion mutants of hepatitis B virus could have an important role in hepatocarcinogenesis in Asian children

Cancer Sci. 2009 Dec;100(12):2249-54. doi: 10.1111/j.1349-7006.2009.01309.x. Epub 2009 Aug 6.

Abstract

Although many studies on the risk factors and their carcinogenesis in adult hepatocellular carcinoma (HCC) have been reported, they remain poorly understood in childhood HCC. A retrospective study of 42 HCC cases in Asian children was conducted. Hepatitis B virus (HBV)-DNA in HCC tissues was detected in 36 of 42 (86%) cases tested, while no hepatitis C virus (HCV)-RNA was detectable in any of HCCs. Twenty of 36 (56%) HCC cases were accompanied by cirrhosis. Surprisingly, very high prevalence of the HBV pre-S deletion mutant was recognized in 27 of 30 (90%) HCCs examined. They occurred most frequently in pre-S2 (20/27, 74%) followed by pre-S1 (5/27, 18.5%), and both pre-S1/S2 (2/27, 7.4%). Interestingly, the pre-S2 mutant consistently appeared with deletion at nt 4-57 in all of the 20 cases with the pre-S2 mutant (100%) and within this locus in the two cases with both pre-S-1/S2 mutants. Type II ground-glass hepatocytes in non-tumorous livers were seen in 15 of the 22 HCCs with the pre-S2 deletion mutant (68%). This hotspot mutation in the pre-S2 was further confirmed by complete genomic sequence of HBV in a Japanese boy who eventually developed HCC. Our result strongly suggests that HBV is a major contributor to the development of HCC in Asian children. The HBV pre-S2 deletion mutant at nt 4-57 which has a CD8 T-cell epitope could be responsible for the emergence and aggressive outcome of childhood HCC. Determination of this hotspot mutation in the pre-S2 region could be a useful index for predicting the clinical outcome of HCC development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / virology
  • Child
  • Child, Preschool
  • Female
  • Gene Deletion*
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B virus / genetics*
  • Humans
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / virology
  • Male
  • Protein Precursors / genetics*

Substances

  • Hepatitis B Surface Antigens
  • Protein Precursors
  • presurface protein 2, hepatitis B surface antigen