Glioma Signaling

Gliomas are one of the most common central nervous system tumors, arising from astrocytes, oligodendrocytes or their precursors. These tumors are graded from I to IV with stage IV or Glioblastoma multiformes (GBM) being the most aggressive of the gliomas. GBMs can form by a de novo pathway to give rise to primary GBMs. Alternatively, through the acquisition of additional mutations, there can be progression from lower grades of glioma to GBM via secondary pathways. (secondary GBM)There are several genetic alterations associated with GBM. In primary GBM, disruption of the p53 pathway often occurs via genetic alterations of ARF or sometimes through amplification of MDM2. Disruptions of the RB pathway occur because of loss of INK4A. Amplification and/or mutation of the epidermal growth factor receptor (EGFR) is the most common genetic defect associated with primary GBM.Tumor initiation in secondary GBM can be triggered by the loss of p53 and activation of the growth-factor-receptor-tyrosine-kinase signaling pathway (such as through overexpression of PDGF/PDGFR). The disruption of the RB pathway contributes to tumor growth progression.Genetic alterations of the tumor suppressor PTEN have been implicated in both pathways, though there seems to be a greater association with primary GBM.