Hereby, there also is a feed-back regulatory loop since p14ARF is negatively regulated by TP53. Hypermethylation of CDKN2A has been frequently observed in low-grade astrocytomas and secondary GBM in about 30% [79] but also in primary GBM in about 50% of the cases. This evidence concerns the gene TP53 and astrocytoma (excluding glioblastoma).