The most malignant grade 4 astrocytoma, or glioblastoma multiforme (GBM), either arises de novo (usually associated to epidermal growth factor receptor pathway activation and PTEN inactivation leading to PI3K kinase/AKT activation pathway) or progresses from lower grade to higher grade over time (characteristically due to p53 and retinoblastoma pathways inactivation). This evidence concerns the gene PTEN and glioblastoma.