In a HCC rat model, the stages of multistage carcinogenesis following initiation are driven primarily by carcinogen-induced epigenetic alterations, including altered global histone lysine methylation patterns; increased histone H3 lysine 9 and histone H3 lysine 27 trimethylation in the promoter regions of the tumor suppressor genes RASSF1A, p16 (INK4a), suppressor of cytokine signaling (SOCS)1, E-cadherin 1 (CDH1)and Cx26, and early RASSF1A; and p16 (INK4a) promoter CpG island hypermethylation. The gene discussed is CDH1; the disease is hepatocellular carcinoma.