All of these findings provide strong evidence demonstrating that a non-catalytic role of EZH2 in MYCN stabilization and tumor progression in vivo, arguing that the enzymatic inhibitors now in clinical development may be impotent in MYC(N)-driven neuroblastomas unless they are capable of depleting EZH2 and/or MYC(N). Here, EZH2 is linked to neuroblastoma.