10013- MPC-3 CHARACTERISTICS AND OUTCOMES OF HISTONE H3 K27M-MUTANT DIFFUSE MIDLINE AND NON-MIDLINE GLIOMAS IN THE KANSAI NETWORK COHORT

Abstract INTRODUCTION Histone H3 K27M-mutant diffuse gliomas are observed at the midline and, rarely, non-midline locations (abbreviated as DMG and NDMG in this study, respectively). It may be unclear how NDMG should be classified in the 2021 WHO classification. This study investigates clinical and molecular characteristics as well as treatment outcomes of patients with NDMG in comparison with those of DMG. METHODS We collected histone H3 K27M-mutant diffuse glioma cases and enrolled in the Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and molecular characteristics and treatment outcomes were analyzed retrospectively and compared between NDMG and DMG cases. RESULTS Anatomical tumor locations were classified into five groups: cerebral hemisphere (16), thalamus (47), brainstem (24), spinal cord (12) and other midline locations (10); therefore, a total of 16 patients with NDMG and 93 patients with DMG were included in this study. Clinical and molecular characteristics of the study cohort (NDMG vs. DMG) included: median age 45 vs. 25 years, female sex (37 vs. 41%), lower-grade histology (6 vs. 56%), preoperative Karnofsky performance status (KPS) scores >80 (50 vs. 49%), resection (50 vs. 36%), adjuvant radiation plus chemotherapy (81 vs. 83%), HIST1H3B p.K27M mutation (0 vs. 4%), TERT promoter mutation (0 vs. 3%), MGMT promoter methylation (25 vs. 9%), BRAF p.V600E mutation (6 vs. 1%), FGFR1 mutation (6 vs. 14%) and EGFR mutation (0 vs. 3%). Median overall survival time was 20.0 vs. 16.6 months. In DNA methylation analysis, NDMG clustered within or close to the reference group of DMG. CONCLUSIONS Diffuse gliomas harboring histone H3 K27M mutation can be observed at cerebral hemisphere in the older adults. NDMG shares many similarities with DMG, suggesting that they correspond to a rare anatomical presentation of DMG.