PRUNE2 and Nijmegen breakage syndrome: Practically, deregulation of the AKT-FOXO3a pathway has a pivotal role in aggressive NB.23 Recent whole-genome sequence analysis of primary NBs revealed that a higher frequency of somatic mutation occurs only in stage 3 and stage 4 of aggressive NBs.37 Considering that the expression level of BMCC1 was very low in high-risk NB,16 such reduced expression of BMCC1 may mediate genomic instability by attenuation of DNA repair and apoptosis through the hyperactivation of AKT followed by the inhibition of FOXO3a.