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Characteristics of H3 K27M-mutant gliomas in adults
David Meyronet1, Maud Esteban-Mader1, Charlotte Bonnet1
1Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neuropathologie, Lyon, Cedex, France; Université Claude Bernard Lyon 1, Lyon, France; Department of Cancer Cell Plasticity, Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France; Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neuro-Oncologie, Lyon, Cedex, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie et Cytologie Pathologiques, Lyon, Cedex, France; CHU Toulouse, Hôpital de Rangueil, Service d'Anatomie et Cytologie Pathologique, Toulouse, France; CHU Toulouse, Hôpital Pierre-Paul Riquet, Service de Neurologie, Toulouse, France; CHU Saint-Etienne, Hôpital Nord, Service d'Anatomie et Cytologie Pathologique, Saint-Etienne, France; CHU de Tours, Hôpital Bretonneau, Service d'anatomie et cytologie pathologiques, Tours, Cedex, France; CHU de Nice, Hôpital Pasteur, Service d'anatomie et cytologie pathologiques, Nice, France; CHU de Nice, Hôpital Pasteur, Service de neurologie, Nice, France; Hospices Civils de Lyon, Groupe Hospitalier Est, Service de Neurochirurgie D, Lyon, Cedex, France; Institut NeuroMyoGene, INSERM 1217/CNRS 5310, Université de Lyon, Lyon, France.
Background:
Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered in adults. The aim of this study was to describe the characteristics of H3 K27M-mutant gliomas in adults.
Methods:
We analyzed the characteristics of 21 adult H3 K27M-mutant gliomas and compared them with those of 135 adult diffuse gliomas without histone H3 and without isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type).
Results:
The median age at diagnosis in H3 K27M-mutant gliomas was 32 years (range: 18-82 y). All tumors had a midline location (spinal cord n = 6, thalamus n = 5, brainstem n = 5, cerebellum n = 3, hypothalamus n = 1, and pineal region n = 1) and were IDH and BRAF-V600E wild type. The identification of an H3 K27M mutation significantly impacted the diagnosis in 3 patients (14%) for whom the histological aspect initially suggested a diffuse low-grade glioma and in 7 patients (33%) for whom pathological analysis hesitated between a diffuse glioma, ganglioglioma, or pilocytic astrocytoma. Compared with IDH/H3 wild-type gliomas, H3 K27M-mutant gliomas were diagnosed at an earlier age (32 vs 64 y, P < .001), always had a midline location (21/21 vs 21/130, P < .001), less frequently had a methylated MGMT promoter (1/21 vs 52/129, P = .002), and lacked EGFR amplification (0/21 vs 26/128, P = .02). The median survival was 19.6 months in H3 K27M-mutant gliomas and 17 months in IDH/H3 wild-type gliomas (P = .3).
Conclusion:
In adults, as in children, H3 K27M mutations define a distinct subgroup of IDH wild-type gliomas characterized by a constant midline location, low rate of MGMT promoter methylation, and poor prognosis.
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