Combining CNAs with MYCN overexpression completely disrupted normal NC differentiation; (ii) Mutant NC cells acquired tumourigenic hallmarks in vitro, the capacity to form tumours in xenografts, and resemble distinct subpopulations of heterogeneous NB tumours; (iii) An extensive re-wiring of chromatin connects the observed transcriptional and functional aberrations with a dysregulated network of developmental TFs. Here, MYCN is linked to neuroblastoma.