Related Experiment Video
Updated: Jul 2, 2025
11:14
Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
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HBV integrations reshaping genomic structures promote hepatocellular carcinoma.
Zhaoyang Qian1,2, Junbo Liang3, Rong Huang3,4
1Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Gut
|February 23, 2024
Summary
Hepatitis B virus (HBV) integrations extensively alter cancer genomes, driving hepatocellular carcinoma (HCC) development. These HBV DNA integrations can lead to early-onset tumors, highlighting their critical role in hepatocarcinogenesis.
Area of Science:
- Genomics
- Oncology
- Hepatology
Background:
- Hepatocellular carcinoma (HCC) is frequently associated with Hepatitis B virus (HBV) integrations.
- Previous research focused on limited HBV integration hotspots, leaving the oncogenic role of other integrations unclear.
Purpose of the Study:
- To investigate the comprehensive impact of HBV integrations on hepatocellular carcinoma (HCC) development.
- To elucidate the mechanisms by which HBV integrations contribute to tumourigenesis.
Main Methods:
- Whole genome sequencing and Nanopore long reads were used to analyze HBV integrations in 124 HCCs.
- A CRISPR-based genetic screen in mouse hepatocytes identified candidate genes involved in HBV integration-mediated oncogenesis.
- CRISPR/Cas9 editing was employed to validate the oncogenic potential of specific amplified genes.
Main Results:
- HBV integrations exhibit complex genomic rearrangements, including bridge-fusion-bridge patterns and translocations.
- These rearrangements are linked to copy number variations in key cancer driver genes (e.g., TERT, CDKN2A/B, TP53, RB1) and early amplifications in chr8q.
- HBV integrations correlate with younger age, higher HBV DNA levels, TP53 mutations, and are less common after antiviral therapy.
- Amplification of TONSL and TMEM65 in chr8q, driven by HBV integration, demonstrated tumourigenic potential in mouse models.
Conclusions:
- HBV integrations significantly reshape host genomes, promoting hepatocarcinogenesis.
- These genomic alterations can occur early in the development of HCC.
- Understanding HBV integration patterns provides insights into HCC pathogenesis and potential therapeutic targets.
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