We observed that H3K27 trimethylation, which was independent of H3K9 dimethylation, was an early event in the silencing of p16INK4a during re-emergence of the tumorigenic profile, a finding that was supported by a number of other groups studying the progression mechanisms of hepatocellular carcinoma (HCC).30, 31, 32 These previous research highlighted the remarkable developmental plasticity of HCC during cancer progression and engendered two important questions. This evidence concerns the gene CDKN2A and cancer.