Fine mapping of hepatitis B virus pre-S deletion and its association with hepatocellular carcinoma.

Naturally occurring pre-S deletion mutants have been identified in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study investigated whether specific deletions within the pre-S region were associated with HCC development. The virologic characteristics of 56 HBV chronic carriers and 112 age-matched patients with HBV-related HCC were examined. The HCC patients had a significantly higher frequency of high viral load, basal core promoter mutation and pre-S deletion than chronic carriers. Sequencing analysis showed that the deleted regions were clustered mainly in the C terminus of pre-S1 (70.5%) and the N terminus of pre-S2 (72.7%) in HCC patients. Immuno-epitope mapping of these pre-S deletion sequences showed that all the deletion regions encompassed T- and B- cell epitopes and the B-cell epitope at amino acid 1-6 of pre-S2 was significantly deleted in HCC patients (60.0% vs. 0.0%; P = 0.036). Functional mapping of these deletion mutants showed that most of HCC patients lost one or more functional sites and the deletion of site for viral secretion (aa 1-5 of pre-S2 domain) was significantly detected in HCC patients than chronic carriers (62.5% vs. 0.0%; P = 0.029). Computational protein function prediction indicated that these mutants may have different molecular functions and participate in other biological processes compared with wild-type pre-S. Deletion of B-cell epitope at amino acid 1-6 of pre-S2 region and the site for virion secretion are significantly associated with the development of HCC in HBV carriers.

Kao JH ，Liu CJ ，Jow GM ，Chen PJ ，Chen DS ，Chen BF ... -  《-》

Different pre-S deletion patterns and their association with hepatitis B virus genotypes.

Chen BF 《-》

High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases.

Chen BF ，Liu CJ ，Jow GM ，Chen PJ ，Kao JH ，Chen DS ... -  《GASTROENTEROLOGY》

Clinical significance of pre-S mutations in patients with genotype C hepatitis B virus infection.

Choi MS ，Kim DY ，Lee DH ，Lee JH ，Koh KC ，Paik SW ，Rhee JC ，Yoo BC ... -  《JOURNAL OF VIRAL HEPATITIS》

Association of pre-S deletion mutant of hepatitis B virus with risk of hepatocellular carcinoma.

Lin CL ，Liu CH ，Chen W ，Huang WL ，Chen PJ ，Lai MY ，Chen DS ，Kao JH ... -  《-》