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Characterization of integrated hepatitis B virus DNA harboring pre-S mutations in hepatocellular carcinoma patients with ground glass hepatocytes
Journal article   Open access   Peer reviewed

Characterization of integrated hepatitis B virus DNA harboring pre-S mutations in hepatocellular carcinoma patients with ground glass hepatocytes

Yih-Ping Su, Selena Y Lin, Ih-Jen Su, Yu-Lan Kao, Shih-Chun Shen, Joshua P Earl, Garth D Ehrlich, Cheng-Yi Chen, Wenya Huang, Ying-Hsiu Su, …
Journal of medical virology, v 96(1), pe29348
Jan 2024
PMID: 38180275
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC10802935/pdf/nihms-1953905.pdfView
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Abstract

pre-S GGH tumor evolution HBV long-read sequencing iDNA
Ground glass hepatocytes (GGHs) have been associated with hepatocellular carcinoma (HCC) recurrence and poor prognosis. We previously demonstrated that pre-S expression in some GGHs is resistant to current hepatitis B virus (HBV) antiviral therapies. This study aimed to investigate whether integrated HBV DNA (iDNA) is the primary HBV DNA species responsible for sustained pre-S expression in GGH after effective antiviral therapy. We characterized 10 sets of micro-dissected, formalin-fixed-paraffin-embedded, and frozen GGH, HCC, and adjacent hepatitis B surface antigen-negative stained tissues for iDNA, pre-S deletions, and the quantity of covalently closed circular DNA. Eight patients had detectable pre-S deletions, and nine had detectable iDNA. Interestingly, eight patients had integrations within the TERT and CCNE1 genes, which are known recurrent integration sites associated with HCC. Furthermore, we observed a recurrent integration in the ABCC13 gene. Additionally, we identified variations in the type and quantity of pre-S deletions within individual sets of tissues by junction-specific PacBio long-read sequencing. The data from long-read sequencing indicate that some pre-S deletions were acquired following the integration events. Our findings demonstrate that iDNA exists in GGH and can be responsible for sustained pre-S expression in GGH after effective antiviral therapy.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Virology
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