Shiou-Hwei YehLi, Chiao LingChiao LingLiLin, You YuYou YuLinMING-CHIH HOWang, Ya ChunYa ChunWangTseng, Sheng TaiSheng TaiTsengPEI-JER CHEN2023-06-282023-06-282023-01-012352345Xhttps://scholars.lib.ntu.edu.tw/handle/123456789/633218Hepatitis 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.enCell-Free Tumor DNA | Hepatitis B Virus | Insertional Mutagenesis | Liver Cancer | Virus-Host Chimera DNA[SDGs]SDG3other10.1016/j.jcmgh.2023.01.001366902972-s2.0-85148366282https://api.elsevier.com/content/abstract/scopus_id/85148366282