Figure 2.

Mechanisms for undermining tumor-suppressive activity of heterozygous IDH1^R132H during glioma progression. (a) In the absence of extracellular glutamate, heterozygous IDH1^R132H, together with intact tumor-suppressor genes (e.g. TP53 and RB), obliterates oncogenic promotion of gliomagenesis. (b) Glutamate in the cerebral cortex negates IDH1^R132H suppression of gliomagenesis, thereby driving anchorage-independent growth and glioma progression, which is further exacerbated by the inactivation of tumor-suppressor genes and the selection against IDH1^R132H heterozygosity. The inhibited events are shaded gray.