Journal Article

DKFZ-2023-01925

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Novel Type of IDH Wild-type Glioma Characterized by Gliomatosis Cerebri-like Growth Pattern, TERT Promoter Mutation, and Distinct Epigenetic Profile.

Muench, A. ; Teichmann, D. ; Spille, D. ; Kuzman, P. ; Perez, E. ; May, S.-A. ; Mueller, W. C. ; Kombos, T. ; Nazari-Dehkordi, S. ; Onken, J. ; Vajkoczy, P. ; Ntoulias, G. ; Bettencourt, C. ; von Deimling, A.DKFZ* ; Paulus, W. ; Heppner, F. L.DKFZ* ; Koch, A.DKFZ* ; Capper, D.DKFZ* ; Kaul, D. ; Thomas, C. ; Schweizer, L.DKFZ*

2023
Ovid [Erscheinungsort nicht ermittelbar]

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Please use a persistent id in citations: doi:10.1097/PAS.0000000000002118

Abstract: Diffuse gliomas in adults encompass a heterogenous group of central nervous system neoplasms. In recent years, extensive (epi-)genomic profiling has identified several glioma subgroups characterized by distinct molecular characteristics, most importantly IDH1/2 and histone H3 mutations. A group of 16 diffuse gliomas classified as 'adult-type diffuse high-grade glioma, IDH-wildtype, subtype F (HGG-F)' was identified by the DKFZ v12.5 Brain Tumor Classifier. Histopathologic characterization, exome sequencing, and review of clinical data was performed in all cases. Based on unsupervised t-distributed stochastic neighbor embedding and clustering analysis of genome-wide DNA methylation data, HGG-F shows distinct epigenetic profiles separate from established central nervous system tumors. Exome sequencing demonstrated frequent TERT promoter (12/15 cases), PIK3R1 (11/16), and TP53 mutations (5/16). Radiologic characteristics were reminiscent of gliomatosis cerebri in 9/14 cases (64%). Histopathologically, most cases were classified as diffuse gliomas (7/16, 44%) or were suspicious for the infiltration zone of a diffuse glioma (5/16, 31%). None of the cases demonstrated microvascular proliferation or necrosis. Outcome of 14 patients with follow-up data was better compared to IDH-wildtype glioblastomas with a median progression-free survival of 58 months and overall survival of 74 months (both P<0.0001). Our series represents a novel type of adult-type diffuse glioma with distinct molecular and clinical features. Importantly, we provide evidence that TERT promoter mutations in diffuse gliomas without further morphologic or molecular signs of high-grade glioma should be interpreted in the context of the clinicoradiologic presentation as well as epigenetic profile and may not be suitable as a standalone marker for glioblastoma, IDH-wildtype.

Note: 2023 Dec 1;47(12):1364-1375

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)
2. DKTK Koordinierungsstelle Frankfurt (FM01)
3. KKE Neuropathologie (B300)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; Allianz-Lizenz ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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