SMAD4 and intrahepatic cholangiocarcinoma: Patients with ICC more frequently harbored IDH1 and PBRM1 mutations, as well amplifications of MYC and MDM2. Notably, we found a potential impact of hepatitis viral (type B or C) infection on mutational frequencies: BTC patients with hepatitis B/C virus infections had significantly lower rates of mutations in TP53, KRAS, ARID1A and SMAD4, with increased rates of mutation in the TERT promoter region and MYC amplification.