TERT promoter mutations are the initial oncogenic events already detected in dysplastic nodules6 whereas alterations in other HCC drivers7–11 involved in cell cycle control (TP53, RB1, CCND1, CDKN2A), Wnt/ß-catenin signaling (CTNNB1, AXIN1), oxidative stress response (NFE2L2, KEAP1) epigenetic regulation (ARID1A, ARID2) and the AKT/mTOR and MAP kinase pathway (RPS6KA3, TSC1, TSC2, PTEN) only occur in progressed HCC12. The gene discussed is RB1; the disease is hepatocellular carcinoma.