https://scholars.lib.ntu.edu.tw/handle/123456789/633218
標題: | Hepatitis B Virus DNA Integration Drives Carcinogenesis and Provides a New Biomarker for HBV-related HCC | 作者: | Shiou-Hwei Yeh Li, Chiao Ling Lin, You Yu MING-CHIH HO Wang, Ya Chun Tseng, Sheng Tai PEI-JER CHEN |
關鍵字: | Cell-Free Tumor DNA | Hepatitis B Virus | Insertional Mutagenesis | Liver Cancer | Virus-Host Chimera DNA | 公開日期: | 1-一月-2023 | 卷: | 15 | 期: | 4 | 來源出版物: | Cellular and Molecular Gastroenterology and Hepatology | 摘要: | Hepatitis B virus (HBV) DNA integration is an incidental event in the virus replication cycle and occurs in less than 1% of infected hepatocytes during viral infection. However, HBV DNA is present in the genome of approximately 90% of HBV-related HCCs and is the most common somatic mutation. Whole genome sequencing of liver tissues from chronic hepatitis B patients showed integration occurring at random positions in human chromosomes; however, in the genomes of HBV-related HCC patients, there are integration hotspots. Both the enrichment of the HBV-integration proportion in HCC and the emergence of integration hotspots suggested a strong positive selection of HBV-integrated hepatocytes to progress to HCC. The activation of HBV integration hotspot genes, such as telomerase (TERT) or histone methyltransferase (MLL4/KMT2B), resembles insertional mutagenesis by oncogenic animal retroviruses. These candidate oncogenic genes might shed new light on HBV-related HCC biology and become targets for new cancer therapies. Finally, the HBV integrations in individual HCC contain unique sequences at the junctions, such as virus-host chimera DNA (vh-DNA) presumably being a signature molecule for individual HCC. HBV integration may thus provide a new cell-free tumor DNA biomarker to monitor residual HCC after curative therapies or to track the development of de novo HCC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/633218 | ISSN: | 2352345X | DOI: | 10.1016/j.jcmgh.2023.01.001 |
顯示於: | 臨床醫學研究所 |
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