Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the 
promoter of telomerase reverse transcriptase (TERT) represent two significant 
discoveries in glioma genomics. Understanding the degree to which these two 
mutations co-occur or occur exclusively of one another in glioma subtypes 
presents a unique opportunity to guide glioma classification and prognosis. We 
analyzed the relationship between overall survival (OS) and the presence of 
IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We 
hypothesized and show that genetic signatures capable of distinguishing among 
several types of gliomas could be established providing clinically relevant 
information that can serve as an adjunct to histopathological diagnosis. We 
found that mutations in the TERT promoter occurred in 74.2% of glioblastomas 
(GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In 
contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, 
but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and 
IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV 
gliomas exhibit TERT promoter mutations alone predominately have primary GBMs 
associated with poor median OS (11.5 months). Patients whose Grade III-IV 
gliomas exhibit IDH1/2 mutations alone predominately have astrocytic 
morphologies and exhibit a median OS of 57 months while patients whose tumors 
exhibit both TERT promoter and IDH1/2 mutations predominately exhibit 
oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing 
gliomas based on their genetic signatures allows for the stratification of these 
patients into distinct cohorts, with unique prognosis and survival.