Genomics of Viral Hepatitis-Associated Liver Tumors
Abstract
:1. Introduction
2. Genomics of Hepatitis B-Related HCC
2.1. HBV Structure and Cell Cycle
2.2. Genomic Landscape of HBV-Related HCC
2.3. HBV Oncogenic Proteins
2.4. HBV Integrations
3. Genomics of Hepatitis C-Related HCC
3.1. HCV Structure and Cell Cycle
3.2. Genomic Landscape of HCV-Related HCC
3.3. HCV Oncogenic Proteins
4. Genomics of Hepatitis D-Related HCC
4.1. HDV Structure and Natural History of Infection
4.2. Genomic Landscape of HDV-Related HCC
5. Interactions with Exposures to Genotoxic Agents
5.1. HBV Infection and Aflatoxin B1 Exposure
5.2. HBV Infection and Aristolochic Acid Exposure
5.3. HDV Infection and Genotoxic Exposures
6. AAV as a New Player in Viral-Associated Liver Tumors
6.1. AAV Structure and Natural History of Infection in the Liver
6.2. AAV-Related Liver Carcinogenesis
7. Conclusions & Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Virus | Genome | Number of Chronic Carriers | Development of Cirrhosis | Development of HCC | Oncogenic Mechanisms | Viral Oncoproteins |
---|---|---|---|---|---|---|
HAV | Single-stranded, positive-sense linear RNA virus | No chronic infection | No | No | -- | -- |
HBV | Partially double-stranded, circular DNA virus | 257 millions | Yes | Yes | Chronic inflammation, oncoprotein, insertional mutagenesis | HBx, altered HBs or HBx |
HCV | Single-stranded, positive-sense linear RNA virus | 71 millions | Yes | Yes | Chronic inflammation, oncoprotein | Core protein, NS3, NS4B, NS5A |
HDV | Single-stranded, negative sense, closed circular RNA virus | 5% of HBV carriers | Yes | Yes | Chronic inflammation, oncoprotein | HDAg |
HEV | Single-stranded, positive-sense linear RNA virus | Only in immuno compromized patient | Only in immuno compromized patient | Exceptionnal (immuno compromized patient) | -- | -- |
AAV2 | Single-stranded DNA virus | 30–80% of positive serology in the general population 26% of AAV2 detected in liver | No | Yes (rare event occurring in normal liver) | Insertional mutagenesis | -- |
Virus | HCC Features | Enriched Mutated Genes | Main Targeted Genes by Viral Integrations |
---|---|---|---|
Hepatitis B | Proliferative HCC, stem cell features, chromosomal instability | TP53 (R249S), IRF2 | TERT, MLL4, CCNE1 |
Hepatitis C | Less agressive, hepatocyte-like features differentiated, chromosomal stability | TERT promoter, CTNNB1 | -- |
Hepatitis D | Genetic instability | SPAT1 | -- |
Adeno-Associated Virus type 2 | -- | PTEN, AXIN1 | CCNA2, CCNE1, GLI1 |
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Péneau, C.; Zucman-Rossi, J.; Nault, J.-C. Genomics of Viral Hepatitis-Associated Liver Tumors. J. Clin. Med. 2021, 10, 1827. https://doi.org/10.3390/jcm10091827
Péneau C, Zucman-Rossi J, Nault J-C. Genomics of Viral Hepatitis-Associated Liver Tumors. Journal of Clinical Medicine. 2021; 10(9):1827. https://doi.org/10.3390/jcm10091827
Chicago/Turabian StylePéneau, Camille, Jessica Zucman-Rossi, and Jean-Charles Nault. 2021. "Genomics of Viral Hepatitis-Associated Liver Tumors" Journal of Clinical Medicine 10, no. 9: 1827. https://doi.org/10.3390/jcm10091827