Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often 
occurs in middle aged patients. Clinically, it is challenging to distinguish A3 
from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape 
of this tumor type, we sequenced the exome of a cohort of A3s (n=16). For 
comparison and to illuminate the genomic landscape of other glioma subtypes, we 
also included in our study diffuse astrocytoma WHO grade II (A2, n=7), 
oligoastrocytoma WHO grade II (OA2, n=2), anaplastic oligoastrocytoma WHO grade 
III (OA3, n=4), and GBM (n=28). Exome sequencing of A3s identified frequent 
mutations in IDH1 (75%, 12/16), ATRX (63%, 10/16), and TP53 (82%, 13/16). In 
contrast, the majority of GBMs (75%, 21/28) did not contain IDH1 or ATRX 
mutations, and displayed a distinct spectrum of mutations. Finally, our study 
also identified novel genes that were not previously linked to this tumor type. 
In particular, we found mutations in Notch pathway genes (NOTCH1, NOTCH2, 
NOTCH4, NOTCH2NL), including a recurrent NOTCH1-A465Tmutation, in 31% (5/16) of 
A3s. This study suggests genetic signatures will be useful for the 
classification of gliomas.