CDKN2A and cancer: Here, we focused on the molecular pharmacological mechanism of PRC2 inhibitors and dissected the critical target genes induced by EED inhibitor MAK683 in sensitive cancer cells deficient in SMARCB1 or ARID1A. PRC2 inhibition by MAK683 induces de-repression of not only CDKN2A/p16, but also GATA4, HLA-B, MMP2/10, ITGA2 and GBP1 with high H3K27me3 around promoters.