PRJNA411908
High-resolution liver cancer genomic profiling links etiology, epigenetic and mutation signatures
Hepatocellular carcinoma (HCC) is a model of diverse spectrum of cancers, since it is induced bywell-known etiologies, mainly Hepatitis C virus (HCV) and Hepatitis B virus (HBV). We exploredthe link between HCV-specific genomic signature and HCV-induced genome-wide epigeneticalterations. Using high-resolution sequencing that detected low-frequency passenger mutations inHCC from three etiology groups – HBV, HCV, or other, we identified novel distinct etiology-dependent mutation signatures. We demonstrated that HCV infection induces epigenetic changes thatpersist as &amp;quot;epigenetic signature&amp;quot; following virus eradication and reprogram host gene expression.High mutation rate associated with HCV etiology correlated with HCV-induced changes inepigenetic markers leading to compacted chromatin. Our study unveils a novel etiology-specificmechanisms leading to cancer, linking etiology to cancer genome.