Post-Treatment Hypermutation In A Recurrent Diffuse Glioma With H3.3 P.G34 Mutation

Diffuse gliomas with H3F3A point mutations affecting histone H3.3 glycine position 34 are a distinct glioma subtype mostly occurring in the cerebral hemispheres of paediatric and young adult patients. These tumours have a high rate of MGMT promoter hypermethylation, a predictive biomarker for response to the DNA alkylating agent temozolomide (TMZ). Post-treatment TMZ-associated hypermutation is a mechanism for TMZ resistance in recurrent isocitrate dehydrogenase (IDH) wildtype glioblastoma and may be seen in association with tumour progression in lower-grade IDH-mutant diffuse astrocytic gliomas.