Fig. 6: Overview of childhood and adult liver malignancies characterized by molecular aberrations and “cell of origin”.
From: Genetic and epigenetic basis of hepatoblastoma diversity
During the process of cell differentiation and maturation from definitive endoderm to hepatoblast and hepatocyte, the expression of ASCL2, a stem cell-related factor, and TERT, an immortality-related gene, is decreased, as well as the self-renewal capacity. Classical hepatoblastoma (HB), derived from hepatoblasts show high activation of Wnt and sustained upregulation of IGF2 due to genetic and epigenetic abnormalities, while adult hepatocellular carcinoma (HCC), derived from mature hepatocytes with low TERT expression, show its upregulation due to promoter mutations and viral integration. Wnt activation (25%) is mostly due to mutations in CTNNB1. TLCT/HCN-NOS shows combined features of both tumors. TERT: telomerase reverse transcriptase, TLCT: translational liver cell tumor, HCN-NOS: hepatocellular malignant neoplasm, not-otherwise-specified.
