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High-Resolution Genomic Profiling of Liver Cancer Links Etiology With Mutation and Epigenetic Signatures
Shira Perez1, Anat Lavi-Itzkovitz2, Moriah Gidoni3
1Molecular Virology Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; Cancer Personalized Medicine, Diagnostic Genomics Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Cellular and Molecular Gastroenterology and Hepatology
|March 25, 2023
Summary
Hepatocellular carcinoma (HCC) research reveals distinct hepatitis C virus (HCV) mutation signatures linked to epigenetic changes. This finding connects mutagenesis to liver cancer risk in chronic HCV patients.
Area of Science:
- Oncology
- Virology
- Genetics
- Epigenetics
Background:
- Hepatocellular carcinoma (HCC) presents a diverse cancer spectrum, often linked to hepatitis B virus (HBV) and hepatitis C virus (HCV) etiologies.
- Understanding etiology-specific mutational patterns is crucial for targeted cancer therapies.
Purpose of the Study:
- To identify hepatitis C virus (HCV)-specific mutational signatures in hepatocellular carcinoma (HCC).
- To explore the relationship between HCV-related mutation rate variations and genome-wide chromatin organization changes induced by HCV infection.
Main Methods:
- High-resolution targeted sequencing of 64 HCC samples across HBV, HCV, and other etiology groups.
- Chromatin immunoprecipitation sequencing (ChIP-seq) for histone modifications (H3K4Me3, H3K9Ac, H3K9Me3) to assess chromatin organization post-HCV infection.
Main Results:
- Identified significant etiology-dependent regional mutation rate variations in 12 genes.
- Observed an enrichment of C->T transversion mutations in HCV-associated HCC.
- Found regional mutation rate variations linked to genomic intervals with HCV-induced epigenetic alterations, potentially affecting base excision repair pathways.
Conclusions:
- Discovered novel, distinct HCV etiology-dependent mutation signatures in HCC associated with altered histone modifications.
- Established a link between mutagenesis and increased liver cancer predisposition in chronic HCV infection.
- Unveiled novel etiology-specific mechanisms contributing to HCC and cancer development.
