Adult diffuse midline gliomas: Clinical, radiological, and genetic characteristics

Diffuse midline gliomas (DMGs) are a diffuse glioma subtype arising from midline brain structures. It is predominantly a disease of childhood; however, it can also occur in adults. Adult DMG has not been previously well described. The aim of this study was to define the characteristics of adult DMG. We described and analyzed the clinical, radiological, and genetic alterations of 9 adult DMGs and compared them with those of 257 non-midline adult high-grade IDH-WT gliomas. The median age of all patients was 38-years old (23-68-years). Most common symptoms were headache, motor/sensory deficit, ataxia, cranial nerve deficit, and confusion. Tumor locations were brainstem (44.5%), thalamus (22.2%), pineal region (22.2%), spinal cord (22.2%), and cerebellum (11.1%). Six-patients (66.7%) were H3 K27M-WT and three (33.3%) were H3 K27M-mutant. In addition to H3 K27M mutations, TP53 gene (55.5%), CDKN2A/B and TERTp (33.3%), PDGFRA (33.3%), PIK3CA, PTEN, KDR, NF1, and MYC (22.2%) were the most frequently mutated genes. Neither IDH1/IDH2 nor EGFR alterations were present. Compared to non-midline high-grade glioma, adult DMG patients were younger (38 vs 61 years, p < 0.001) and lacked EGFR-alterations (0/9 vs 123/257, p = 0.004). The median survival of DMG and non-midline high-grade gliomas was 19 and 18 months respectively (p = 0.964). Our data support that adult DMGs have different oncogenic drivers compared to non-midline high-grade gliomas. Regardless of H3 K27M mutation status, neither of the nine adult DMG cases demonstrated IDH1/IDH2 or EGFR alterations. Larger multi-institutional studies are needed to further characterize the biology of this rare type of diffuse glioma in adults.