INTRODUCTION: Mutations in H3F3A, which encodes histone H3.3, commonly occur in 
pediatric glioblastoma. Additionally, H3F3A K27M substitutions occur in gliomas 
that arise at midline locations (eg, pons, thalamus, spine); moreover, this 
substitution occurs mainly in tumors in children and adolescents. Here, we 
sought to determine the association between H3F3A mutations and adult thalamic 
glioma.
METHODS: Genomic H3F3A was sequenced from 20 separate thalamic gliomas. 
Additionally, for 14 of the 20 gliomas, 639 genes--including cancer-related 
genes and chromatin-modifier genes--were sequenced, and the Infinium 
HumanMethylation450K BeadChip was used to examine DNA methylation across the 
genome.
RESULTS: Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 
11 were from patients under 50 years of age (median age, 38 y; range, 17-46), 
and 7 were from patients over 50 years of age. The H3F3A K27M mutation was 
present in 10 of the 11 (91%) younger patients and absent from all 7 older 
patients. Additionally, H3F3A K27M was not detected in the 2 diffuse 
astrocytomas. Further sequencing revealed recurrent mutations in TP53, ATRX, 
NF1, and EGFR. Gliomas with H3F3A K27M from pediatric or young adult patients 
had similar, characteristic DNA methylation profiles. In contrast, thalamic 
gliomas with wild-type H3F3A had DNA methylation profiles similar to those of 
hemispheric glioblastomas.
CONCLUSION: We found that high-grade thalamic gliomas from young adults, like 
those from children and adolescents, frequently had H3F3A K27M.