Until recently, mutations in histones had not been described in any human 
disease. However, genome-wide sequencing of pediatric high-grade gliomas 
revealed somatic heterozygous mutations in the genes encoding histones H3.1 and 
H3.3, as well as mutations in the chromatin modifiers ATRX and DAXX. The 
functional significance and mechanistic details of how these mutations affect 
the tumors is currently under intensive investigation. The information gained 
from these studies will shed new light on normal brain development as well as 
increase our understanding of the tumorigenic processes that drive pediatric 
high-grade gliomas.