PTEN and central nervous system cancer: In GBM, this pathway is activated by two frequent alterations, an in-frame deletion of amino acids 6–273 in EGFRvIII resulting in a mutant EGFR protein which is present in more than 50% of high grade gliomas and its activation is ligand-independent [79] and oncogenic mutations in PTEN detected in up to 40% of adult gliomas [80].