High frequency of H3 K27M mutations in adult midline gliomas

  • Azadeh EbrahimiEmail author
  • Marco Skardelly
  • Martin U. Schuhmann
  • Martin Ebinger
  • David Reuss
  • Manuela Neumann
  • Ghazaleh Tabatabai
  • Patricia Kohlhof-Meinecke
  • Jens SchittenhelmEmail author
Original Article – Cancer Research



Diffuse midline gliomas, H3 K27M-mutant were introduced as a new grade IV entity in WHO classification of tumors 2016. These tumors occur often in pediatric patients and show an adverse prognosis with a median survival less than a year. Most of the studies on these tumors, previously known as pediatric diffuse intrinsic pontine glioma, are on pediatric patients and its significance in adult patients is likely underestimated.


We studied 165 cases of brain tumors of midline localization initially diagnosed as diffuse astrocytomas, oligodendrogliomas, pilocytic astrocytomas, supependymomas, ependymomas and medulloblastomas in patients with an age range of 2–85.


We identified 41 diffuse midline gliomas according WHO 2016, including 12 pediatric and 29 adult cases, among them two cases with histological features of low grade tumors: pilocytic astrocytoma and subependymoma. 49% (20/41) of the patients were above 30 years old by the first tumor manifestation including 29% (11/41) above 54 that signifies a broader age spectrum as previously reported. Our study confirms that H3 K27M mutations are associated with a poorer prognosis in pediatric patients compared to wild-type tumors, while in adult patients these mutations do not influence the survival significantly. The pattern of tumor growth was different in pediatric compared to adult patients; a diffuse growth along the brain axis was more evident in adult compared to pediatric patients (24% vs. 15%).


H3 K27M mutations are frequent in adult midline gliomas and have a prognostic role similar to H3 K27M wild-type high-grade tumors.


Diffuse midline glioma H3F3A H3 K27M mutations 



JS is supported by a Grant from the Else Uebelmesser Foundation for Applied Cancer Research, Tuebingen, Germany. GT served on Advisory Boards of BMS, Roche Switzerland, MSD Switzerland, received travel grants from Roche Switzerland, MSD Switzerland, Medac; received research support/Grants from Roche Diagnostics and Medac.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of TuebingenEberhard Karls University of TuebingenTuebingenGermany
  2. 2.Clinical Cooperation Unit NeuropathologyGerman Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department of Neurosurgery, University Hospital of TuebingenEberhard Karls University of TuebingenTuebingenGermany
  4. 4.Interdisciplinary Division of Neurooncology, Departments of Vascular Neurology and Neurosurgery, University Hospital of TuebingenEberhard Karls University of TuebingenTuebingenGermany
  5. 5.Laboratory for Clinical and Experimental NeurooncologyHertie-Institute for Clinical Brain ResearchTuebingenGermany
  6. 6.Center for Personalized MedicineEberhard Karls University of TuebingenTuebingenGermany
  7. 7.German Consortium for Translational Cancer Research (DKTK), DKFZ Partner Site TuebingenTuebingenGermany
  8. 8.Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart, University Hospital of TuebingenEberhard Karls University of TuebingenTuebingenGermany
  9. 9.Department of General Pediatrics, Hematology/OncologyUniversity Children’s HospitalTuebingenGermany
  10. 10.Department of Neuropathology, Institute of PathologyUniversity Hospital of HeidelbergHeidelbergGermany
  11. 11.Department of PathologyKatharinenhospital StuttgartStuttgartGermany

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