SMAD4 and intrahepatic cholangiocarcinoma: In the present study, we found that seven most recurrent mutations (TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus and BAP1) showed pair-wise co-occurrences or mutual exclusivities in ICC, and could aggregate into three genomic clusters with distinct clinicopathological and molecular features, biological behaviors and therapeutic vulnerabilities.