In addition, liver fluke-associated CCA and non-liver fluke-associated CCA appear to have different mutational profiles; liver fluke-associated CCA displays a higher frequency of erb-b2 receptor tyrosine kinase 2 (ERBB2) gene amplification and TP53, and SMAD family member 4 (SMAD4) mutations, and fluke-negative CCA display programmed cell death 1 ligand 1 (PD-L1)/programmed cell death 1 ligand 2 (PD-L2) protein expression, mutations in IDH1/2 and breast-cancer susceptibility gene 1-associated protein 1 (BAP1), and FGFR-related gene rearrangements [8, 10, 11]. The gene discussed is SMAD4; the disease is cholangiocarcinoma.