Thus, sharing the feedback upregulation of Wnt-targeted genes with colorectal cancer could explain the unique feature of Wnt activation in HB rather than in HCC, and may imply that their “cell of origin” is derived from the ASCL2-positive premature hepatoblast, similar to the intestinal epithelial cells, which have high proliferative potential. Here, ASCL2 is linked to hepatocellular carcinoma.