Additionally, the CCA-specific DNA alterations, IDH1/2 and BAP1, could be driving this transdifferentiation process in the absence of classical HCC mutations such as CTNNB1 and TP53. Artegiani et al. recently reported that BAP1−/− organoids upregulated EPCAM while downregulating liver-specific genes, consistent with our findings (Supplementary Fig. 4a)42. This evidence concerns the gene CTNNB1 and cholangiocarcinoma.