Characteristics and outcomes of diffuse non-midline gliomas with H3F3A gene mutation in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort study.

Diffuse gliomas with H3F3A gene mutation such as H3.3 K27M and G34R/V are infrequently found in the cerebral hemisphere. These tumors may be called histone H3 K27M-mutant diffuse non-midline gliomas (NDMG) or H3 G34-mutant diffuse hemispheric gliomas (DHG), respectively. We investigated the clinical, radiological and molecular characteristics and treatment outcomes of patients with H3 K27-mutant NDMG compared with those with H3 G34-mutant DHG. We collected cases of histone H3-mutant diffuse glioma at non-midline location that were enrolled in the Kansai Molecular Diagnosis Network for CNS Tumors. The clinical, radiological and pathological characteristics and DNA methylation were retrospectively analyzed and then compared between cases of NDMG and DHG. We evaluated various factors to examine their effects on overall survival. Included in this study were 16 patients with H3 K27M-mutant NDMG and nine patients with H3 G34R/V-mutant DHG. Patients with NDMG were older than those with DHG (median age: 45 vs. 25 years old). Overall survival times of patients with NDMG were comparable to those of DHG (median overall survival: 20.0 vs. 22.5 months). Female sex, preoperative Karnofsky performance status score ≥ 80 and extensive surgical resection tended be related to better prognoses in the patients with these tumors. H3 K27M-mutant NDMGs were shown to possess similar DNA methylation properties to H3 K27M-mutant DMGs. Diffuse gliomas harboring histone H3 K27M mutation can arise in the cerebral hemisphere in older adults. These findings suggest that H3 K27M-mutant NDMGs show different clinical manifestations to H3 K27M-mutant DMGs and H3 G34R/V-mutant DHGs, despite having similar molecular properties to H3 K27M-mutant DMGs.