JOURNAL ARTICLE

High frequency of H3 K27M mutations in adult midline gliomas

Azadeh Ebrahimi, Marco Skardelly, Martin U Schuhmann, Martin Ebinger, David Reuss, Manuela Neumann, Ghazaleh Tabatabai, Patricia Kohlhof-Meinecke, Jens Schittenhelm
Journal of Cancer Research and Clinical Oncology 2019 January 4
30610375

PURPOSE: 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.

METHODS: 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.

RESULTS: 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%).

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

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