In the well-established rat model of HCC induced by diethylnitrosamine (DEN) and other chemicals, it was shown that Gankyrin overexpression, pRb degradation, and the hypermethylation of CDKN2A and TP53 are the initiating events that promote the multistep process of hepatocarcinogenesis14, 16, 19. The gene discussed is RB1; the disease is hepatocellular carcinoma.