A Novel Type of IDH-wildtype Glioma Characterized by Gliomatosis Cerebri-like Growth Pattern, TERT Promoter Mutation, and Distinct Epigenetic Profile.
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 12 2023
01 12 2023
Historique:
medline:
15
11
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37737691
doi: 10.1097/PAS.0000000000002118
pii: 00000478-990000000-00233
doi:
Substances chimiques
Isocitrate Dehydrogenase
EC 1.1.1.41
Telomerase
EC 2.7.7.49
TERT protein, human
EC 2.7.7.49
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1364-1375Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: Supported by a Deutsches Konsortium für Translationale Krebsforschung (DKTK) Young Investigator grant to L.S. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
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