The tumor’s mutational burden and the occurrence of specific genetic alterations (e.g., affecting tyrosine kinase signaling like FGFR, HER2, KRAS, FGFR2 fusions, or the IDH pathway, as well as chromatin-remodeling genes like ARID1A) correlate with the CCA’s anatomic localization within the biliary tract system. Here, IDH2 is linked to cholangiocarcinoma.