SMAD4 and cancer: As examples, (1) extrahepaticCCAs have more SMAD4 mutations than iCCAs (Churi et al., 2014; Onget al., 2012); (2) a Chinese study found a much lower incidence ofIDH (5%), PBRM1 (1%), andBAP1 (1%) mutations (Zou et al., 2014) in iCCAs; and (3) liver fluke- and/or viralhepatitis-positive cancers have a higher incidence of TP53mutations and lower incidence of IDH mutations (Chan-On et al., 2013; Onget al., 2012; Zou et al., 2014).In this study, we focused on intrahepatic and fluke- and hepatitis-negative CCA,which minimized heterogeneity and improved the ability to apply categorizingstatistics.