In RB1−/− retinoblastoma, amplification and high expression of TP53 negative regulators MDM4 and MDM2 and loss of the MDM2 inhibitor p14ARF have been proposed as alternative mechanisms of p53 inactivation of its tumor suppresor function as the genetic inactivation of TP53 itself were only reported anecdotally [2,5,35,36,37,38,39,40]. This evidence concerns the gene MDM4 and retinoblastoma.