In two inferred evolutionary models, PI3K pathway drives the gliomagenesis as a consequence of PTEN truncal inactivation or PI3K activating genetic mutations, whereas the tumor progression is sustained by the over-activation of RTK/RAS signaling through the occurrence of subclonal NF1 and EGFR alterations in C1 and C2 models, respectively. This evidence concerns the gene PIK3CA and neoplasm.