Intra-tumoral epigenetic heterogeneity and aberrant molecular clocks in hepatocellular carcinoma.

ABSTRACT: There is limited understanding of the epigenetic drivers of tumor evolution in hepatocellular carcinoma (HCC). Here we characterize the epigenetic contribution of methylation to intra-tumoral heterogeneity (mITH) using regional enhanced reduced-representation bisulfite sequencing DNA methylation data from 47 early stage, treatment-naive HCC biopsies across 9 patients by quantifying regional differential methylation across promoters and CpG islands, while overlapping with methylation age markers. Furthermore, we integrate these data with matching RNA-sequencing, targeted DNA sequencing, tumor-infiltrating lymphocyte (TIL), and hepatitis-B viral expression data. We found substantial mITH signatures in promoter and enhancer sites across 44% of patients in our cohort that highlight a novel axi

SUBMITTER: Restrepo P 

PROVIDER: S-EPMC12633114 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature