Molecular characteristics of H3 K27M mutation gliomas in Chinese adults.

Abstract

e14018 Background: Diffuse midline glioma H3 K27M–mutant is a specific entity added to the 2016 update of the WHO classification of CNS tumors. H3K27M-mutant gliomas are diagnosed primarily in children and adolescents with TP53 and/or ATRX mutations. However, the characteristics of H3 K27M-mutant gliomas in adults have not been explicitly described. Methods: We performed the 131-gene panel targeted sequencing on tumor samples from 33 adults H3 K27M-mutant gliomas( > 18 years) and 13 children and adolescents H3 K27M-mutant gliomas(≤18 years) in a CAP certified laboratory. Somatic mutations, copy number variations, and fusion genes were detected following the standard operating procedure (SOP). The MS-based assay measured MGMT promoter methylation. We calculated the tumor location and the median age in different cohorts. Results: In our adult cohort, 22/33（66.7%）had a midline location（spinal cord n = 2, thalamus n = 7, brainstem n = 6, cerebellum n = 3, pineal region n = 1, Basal ganglia region n = 3）, 6/33（18.1%）had a non-midline location (Lateral ventricle n = 2, Cerebral hemispheres n = 4). In the children and adolescents cohort, 11/13（84.6%）occurred in midline location, 1/13(7.7%) occurred in the Lateral ventricle. MGMT promoter methylation did not differ in adult and pediatric H3 K27M-mutant gliomas (12.1% vs. 0). H3 K27M-mutant adult gliomas significantly co-occurred with the NF1 mutation(P = 0.008937). The median age of H3 K27M-mutant adult gliomas with NF1 modification (13/33, 39.4%) is higher than the NF1 wild type (49 years vs. 38 years, P = 0.107), although the difference has no statistical significance. Conclusions: In Chinese adults, as in children, H3 K27M mutation gliomas are characterized by a constant midline location, low rate of MGMT promoter methylation. Inconsistently, H3 K27M mutant adult gliomas are featured by a higher rate of NF1 mutations. Our molecular profiling analysis revealed the H3 K27M mutation in adult gliomas. Our research suggests potential molecular pathogenesis of H3K27M mutant adult gliomas and identifies more therapeutic targets for precision medicine.