The unbalanced state produced by either loss-of-function BAF subunit mutations or gain-of-function PRC2 mutations might be an effective site for therapeutic intervention (Fig. 5). Several studies have indicated that EZH2 inhibition to a level that removes nearly all H3K27Me3 over the genome leads to death of cells having a BAF47 mutation (110, 111). Although one would anticipate substantial toxicity associated with removal of PRC2 function, mice appeared to tolerate the treatment, and their tumors underwent regression with EZH2 inhibition. Also, a diffuse large cell lymphoma with activating mutations in Ezh2 (Y641F/N) appears to be sensitive to Ezh2 inhibition (112).
