The first whole exome sequencing study of 8 liver-fluke related CCA identified 206 somatic mutations in 187 genes, including novel genes (e.g. SMAD4 (16.7%), roundabout guidance receptor 2 (ROBO2) (9.3%), GNAS (9.3%), MLL3 (14.8%), Cyclin-dependent kinase inhibitor 2A (CDKN2A) (5.6%), paternally expressed 3 (PEG3) (5.6%), ring fingers proteins (RNF) (9.3%) [22]. Here, SMAD4 is linked to cholangiocarcinoma.