Expression of the proliferation marker MKI67 was found to be augmented in NOTCH1/RBPJ mutant brain tumors with low HES/HEY expression levels [134], and NOTCH mutations were a high-risk factor associated with shorter patient survival [135], suggesting that NOTCH signaling inhibition contributes to increased glioma aggressiveness. The gene discussed is NOTCH1; the disease is glioma.