In the preneoplastic livers of PML−/−HBsAgtg/0 mice by 3 months of age, we observed an exceptionally high prevalence (>50%) of mutations in the cancer drivers Ctnnb1 (which encodes β-catenin of the Wnt signaling cascade), Trp53 (which encodes p53 and maintains genomic integrity), Cdk4 (which drives cell cycle progression) and Mllt4 (which contributes to chromatin remodeling). Here, TP53 is linked to cancer.