LGGs arise from mutations in genes whose protein products regulate RAS pathway signaling. In this manner, mutations in genes encoding receptor tyrosine kinases (RTK), which transduce extracellular signals, as well as the downstream effectors PTPN11, RAS, BRAF/RAF, and lead to hyperactivation of mitogenic signaling downstream through the MAP kinase and PI3-kinase pathways. In addition, mutational inactivation of the neurofibromatosis type 1 (NF1) tumor suppressor gene results in increased RAS activity. MEK and AKT can shorten G1 transition through mammalian target of rapamycin (mTOR)-dependent and -independent signaling. The presence of stromal growth factors and chemokines in the tumor microenvironment transduce signals through tumor cell receptors and further enhance glioma growth in a paracrine fashion. Reported mutations are denoted in green.