Targeting H3.3 mutated pediatric high grade gliomas – A high throughput screening approach to identify novel therapeutic agents

Pediatric high grade gliomas (pHGG) are among the most common malignant brain tumors in childhood and account for the majority of cancer related mortality in this age group. The recent discovery of two recurrent mutations in the tail of histone variant H3.3, resulting either in a substitution of Glycine at position 34 (G34R/V) or Lysine at position 27 (K27 M), has deepened our understanding of this tumor entity and led to a new molecular classification system. However, the functional consequences of these mutations on the tumor biology remain largely unknown. Consequently, no potential drug targets could be deli…