Distinct molecular profile and outcome of oligodendroglioma, IDH-mutant, 1p/19q-codeleted, and TERTp-wildtype: A grade 1 oligodendroglioma of young patients?
Nozzoli F, Rahmanzade R, Schmid S, Schweizer L, Schrimpf D, Friedel D, Gobel K, Reuss DE, Banan R, Sievers P, Pusch S, Bogumil H, Hinz F, Suwala AK, Aras FK, Friedrich L, Osella-Abate S, Ricci AA, Macciotta A, Simon T, Fleischhack G, Keyvani K, Hansford JR, Khuong-Quang DA, Schucht P, Maragkou T, Juratli TA, Meinhardt M, Zechel S, Stadelmann C, Coras R, Sakowitz OW, Goeppert B, Schittenhelm J, Etminan N, Ratliff M, Herold-Mende C, Pfister SM, Wick W, Krieg SM, Von Deimling A, Sahm F, Bertero L (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Book Volume: 27
Pages Range: 2711-2725
Journal Issue: 10
Abstract
Background Oligodendrogliomas, characterized by isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletion, often exhibit telomerase reverse transcriptase promoter (TERTp) mutations, which have been linked to telomere maintenance (TM) and tumor proliferation. Although there are a few reports on a TERTp-wildtype subset of these tumors in adolescents and young adults, the frequency, molecular characteristics, and prognostic implications of TERTp-wildtype status in oligodendrogliomas remain elusive. Methods We retrospectively analyzed 166 IDH-mutant and 1p/19q-codeleted oligodendroglioma cases through comprehensive histopathological review and molecular analyses, including Sanger sequencing, DNA methylation profiling, and whole-exome sequencing (WES). Results A TERTp-wildtype status was observed in 20/166 cases (12.0%) and was significantly associated with noticeably young age (age range: 14-27, P < .001), CNS WHO grade 2 (P = .003), and the absence of additional DNA copy number variations (CNVs) beyond the pathognomonic 1p/19q codeletion (P < .001). Epigenetic profiling demonstrated TERTp-wildtype tumors shaped a distinct subgroup at the utmost periphery of TERTp-mutant oligodendrogliomas. Methylation analysis of the upstream and proximal TERTp regions revealed that, in line with the absence of genetic alterations, epigenetic regulation does not favor TERT overexpression in TERTp-wildtype oligodendrogliomas. WES showed no TM-related gene alterations in TERTp-wildtype cases. Cox regression analysis confirmed TERTp-wildtype status as an independent prognostic factor for more favorable progression-free survival (PFS) (P = .009). Conclusions In conclusion, "oligodendroglioma, IDH-mutant, 1p/19q-codeleted, and TERTp-wildtype"represent a distinct molecular subgroup associated with younger age and a better clinical course compared to CNS WHO grade 2 oligodendrogliomas.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Heidelberg
Germany (DE)
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Hopp-Kindertumorzentrum Heidelberg - KiTZ
Germany (DE)
University of Turin / Università degli Studi di Torino (UNITO)
Italy (IT)
Universitätsklinikum Essen
Germany (DE)
Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim)
Germany (DE)
University of Adelaide
Australia (AU)
The Royal Children's Hospital Melbourne
Australia (AU)
Inselspital, Universitätsspital Bern
Switzerland (CH)
Universität Bern
Switzerland (CH)
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Universitätsklinikum Göttingen
Germany (DE)
Regionale Kliniken Holding RKH
Germany (DE)
Universitätsklinikum Tübingen
Germany (DE)
Careggi University Hospital / Azienda Ospedaliero Universitaria Careggi
Italy (IT)
Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Italy (IT)
Germany (DE)
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Hopp-Kindertumorzentrum Heidelberg - KiTZ
Germany (DE)
University of Turin / Università degli Studi di Torino (UNITO)
Italy (IT)
Universitätsklinikum Essen
Germany (DE)
Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim)
Germany (DE)
University of Adelaide
Australia (AU)
The Royal Children's Hospital Melbourne
Australia (AU)
Inselspital, Universitätsspital Bern
Switzerland (CH)
Universität Bern
Switzerland (CH)
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Universitätsklinikum Göttingen
Germany (DE)
Regionale Kliniken Holding RKH
Germany (DE)
Universitätsklinikum Tübingen
Germany (DE)
Careggi University Hospital / Azienda Ospedaliero Universitaria Careggi
Italy (IT)
Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Italy (IT)
How to cite
APA:
Nozzoli, F., Rahmanzade, R., Schmid, S., Schweizer, L., Schrimpf, D., Friedel, D.,... Bertero, L. (2025). Distinct molecular profile and outcome of oligodendroglioma, IDH-mutant, 1p/19q-codeleted, and TERTp-wildtype: A grade 1 oligodendroglioma of young patients? Neuro-Oncology, 27(10), 2711-2725. https://doi.org/10.1093/neuonc/noaf141
MLA:
Nozzoli, Filippo, et al. "Distinct molecular profile and outcome of oligodendroglioma, IDH-mutant, 1p/19q-codeleted, and TERTp-wildtype: A grade 1 oligodendroglioma of young patients?" Neuro-Oncology 27.10 (2025): 2711-2725.
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