Ten cases with ICC had a number of non-silent mutations in the known biliary tract cancer driver genes [18], such as SMAD4 (mutated in three cases), BAP1 (two cases), NRAS (two cases), TP53 (two cases), ELF3 (one case), CDKN2A (one case), FGFR3 (one case), GNAS (one case), IDH1 (one case), PIK3CA (one case) and RPL22 (one case) (Fig. 1b). This evidence concerns the gene SMAD4 and biliary tract cancer.