APC and intrahepatic cholangiocarcinoma: In Trp53;Nf2 codeleted cancers, we observed upregulation of Wnt9b and suppression of inhibitors of Wnt signaling Nkd2 and Sfrp2, suggesting that alterations in ligand levels and negative regulators of Wnt signaling are important mediators of ICC progression and that these cancers form independent of core Wnt-activating mutations in Apc, Axin2, and Ctnnb1 (36).