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Genomics of Viral Hepatitis-Associated Liver Tumors

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JOURNAL OF CLINICAL MEDICINE
卷 10, 期 9, 页码 -

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MDPI
DOI: 10.3390/jcm10091827

关键词

hepatitis B; adeno associated virus type 2; genetic alterations; hepatitis delta

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Virus-related liver carcinogenesis, including chronic hepatitis B and C infections, is a major contributor to cancer-related deaths worldwide. Mechanisms such as chronic inflammation and cirrhosis, viral insertional mutagenesis, and expression of oncogenic proteins play key roles in the oncogenic properties of HBV infection. Additionally, adeno associated virus type 2 (AAV2) insertion mutagenesis has been linked to the occurrence of HCC in non-cirrhotic patients.
Virus-related liver carcinogenesis is one of the main contributors of cancer-related death worldwide mainly due to the impact of chronic hepatitis B and C infections. Three mechanisms have been proposed to explain the oncogenic properties of hepatitis B virus (HBV) infection: induction of chronic inflammation and cirrhosis, expression of HBV oncogenic proteins, and insertional mutagenesis into the genome of infected hepatocytes. Hepatitis B insertional mutagenesis modifies the function of cancer driver genes and could promote chromosomal instability. In contrast, hepatitis C virus promotes hepatocellular carcinoma (HCC) occurrence mainly through cirrhosis development whereas the direct oncogenic role of the virus in human remains debated. Finally, adeno associated virus type 2 (AAV2), a defective DNA virus, has been associated with occurrence of HCC harboring insertional mutagenesis of the virus. Since these tumors developed in a non-cirrhotic context and in the absence of a known etiological factor, AAV2 appears to be the direct cause of tumor development in these patients via a mechanism of insertional mutagenesis altering similar oncogenes and tumor suppressor genes targeted by HBV. A better understanding of virus-related oncogenesis will be helpful to develop new preventive strategies and therapies directed against specific alterations observed in virus-related HCC.

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