described mutations collectively leading to PI3K and MAPK hyperactivation in ∼90% of human gliomas. Therefore, we additionally generated iNPCs-overexpressing mutant-active versions of Src (to mimic infiltrative behaviour), EGFR (duplicated and/or mutated in ∼57% of human gliomas)21 and Ras (mutated in ∼1% of human gliomas and a common upstream regulator of both PI3K and MAPK signalling)21. Lentivirus-mediated overexpression of the different mutant genes in either 293T cells or WT- and p53KD- iNPCs (namely Ras/EGFR/SrciNPCs and p53KD-Ras/EGFR/SrciNPCs, respectively) confirmed the hyperactivation of PI3K and MAPK pathways as demonstrated by increased AKT and ERK phosphorylation, respectively (Supplementary Fig. 2a,e,f).
