BACKGROUND: Glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma 
(DIPG) belong to the most aggressive cancers in children with poor prognosis and 
limited therapeutic options. Therapeutic targeting of epigenetic proteins may 
offer new treatment options. Preclinical studies identified Enhancer of Zeste 
Homolog 2 (EZH2) within polycomb repressor complex 2 (PRC2) as a potential 
epigenetic anti-tumor target in adult GBM cells but similar inhibition studies 
in pediatric GBM/DIPG were still missing. Moreover, approximately 30% of 
pediatric high grade gliomas (pedHGG) including GBM and DIPG harbor a lysine 27 
mutation (K27M) in histone 3.3 (H3.3) which is correlated with poor outcome and 
was shown to influence EZH2 function.
PATIENTS, MATERIALS AND METHODS: The present study investigated the correlation 
of expression of EZH2 and other PRC2 genes (EZH1, SUZ12, EED) with overall 
survival of pediatric GBM patients and the cytotoxic impact of EZH2 inhibition 
by the novel agent Tazemetostat in pediatric GBM/DIPG cells harboring either a 
H3.3 mutation or a H3 wildtype.
RESULTS: EZH2 gene expression does not correlate with survival of pedHGG 
patients, and EZH2 inhibition does not induce significant cytotoxicity in pedHGG 
cells independently of H3.3 mutations.
DISCUSSION AND CONCLUSION: We suggest that EZH2 inhibition might not offer an 
effective single agent treatment option for paedHGG patients. However, the 
therapeutic efficacy in combination with cytotoxic and/or other epigenetically 
active agents still has to be elucidated.