RB1 and hepatocellular carcinoma: Among them, alterations of the cyclin D-CDK4/6-Rb pathways frequently occur in HCC: CDK4 overexpression has been described in more than 70% of cases (12), whereas the inactivation of CDKN2A/ARF gene, encoding for the cell cycle inhibitor p16INK4a, has been found in over 50% of patients (13, 14).