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. Here, MDM2 is linked to infection.