Case Report: Identification of rare H3-3A p.G35W variant in a case of adolescent tectal plate low-grade glioma

The treatment of paediatric low-grade gliomas has been previously controversial as to whether upfront surgery or a conservative approach should be utilised, with a recent paradigm shift favouring biopsy or resection, if possible, and early treatment. Pilocytic astrocytomas are a subset of low-grade glioma with favourable prognoses. Here, we present the case of an adolescent who underwent a stereotactic endoscopic biopsy of a tectal plate lesion, classified as a pilocytic astrocytoma. Due to the intricate nature of this tumour, methylation and targeted sequencing were performed, which identified a rare H3-3A p.G35W(G34W) variant. This variant has been predominantly identified in giant cell tumours of the bone, with isolated reports in spinal cord astrocytomas. In the current WHO Classification of Tumours of the Central Nervous System, diffuse hemispheric glioma, H3 G34-mutant is recognised as a distinct tumour type with frequent TP53, PDGFRA, and-ATRX and DAXX alterations and is associated with aggressive behaviour. The histone H3 variant (H3-3A p.G35W) detected in our patient has not been previously characterised in tectal plate gliomas, rendering it an unclear predictor of tumour behaviour. In this case study, we discuss the importance of methylation profiling and the potential implications of H3 G34-mutant gliomas.