MYCN-amplification-induced overexpression of the ubiquitin ligase mouse double minute 2 (MDM2), that targets p53 for degradation, is one proposed mechanism contributing to this treatment resistance [24,25], while in MYCN-wild-type tumours, overexpression of the epigenetic regulator and histone methyltransferase SETD8, that also methylates and inactivates p53, was linked to high-risk neuroblastoma [26]. This evidence concerns the gene TP53 and neuroblastoma.