Abstract
BACKGROUND
Diffuse midline glioma (DMG), H3 K27M-altered is a central nervous system tumor that occurs predominantly in children and young adults. They are characterized by distinct epigenetic features, whose therapeutic consequences remain ill defined.
MATERIAL AND METHODS
In this retrospective multicenter cohort study 52 adult patients with H3 K27M-mutant DMG and matched H3-wildtype glioma were characterized with respect to location, radiological features, methylation profile and clinical course.
RESULTS
DMGs were predominantly located in the thalamus, brainstem or spinal cord, but also occurred in the cerebellum and cerebral hemispheres. 35% of H3 K27M-mutant gliomas did not show contrast enhancement on MRI and only 43% had central necrosis. A third of adult H3 K27M-mutant gliomas, especially in spinal location, had distant progression resulting in shorter progression free survival (PFS). Addition of alkylating chemotherapy with temozolomide to radiotherapy did not result in prolonged PFS or overall survival (OS). A distinct methylation signature on the q arm of chromosome 15 differentiated patients with favorable OS form patients with short OS.
CONCLUSION
Adult DMGs occur throughout the CNS and are characterized by distinct epigenetic, radiological and clinical features.