Distinct molecular profile and outcome of oligodendroglioma, IDH-mutant, 1p/19q-codeleted, and TERTp-wildtype: a grade 1 oligodendroglioma of young patients?
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-wil...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 July 2025
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| In: |
Neuro-Oncology
Year: 2025, Pages: 1-15 |
| ISSN: | 1523-5866 |
| DOI: | 10.1093/neuonc/noaf141 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/noaf141
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| Author Notes: | Filippo Nozzoli, Ramin Rahmanzade, Simone Schmid, Leonille Schweizer, Daniel Schrimpf, Dennis Friedel, Kirsten Göbel, David E. Reuss, Rouzbeh Banan, Philipp Sievers, Stefan Pusch, Henri Bogumil, Felix Hinz, Abigail K. Suwala, Fuat Kaan Aras, Lukas Friedrich, Simona Osella-Abate, Alessia Andrea Ricci, Alessandra Macciotta, Thorsten Simon, Gudrun Fleischhack, Kathy Keyvani, Jordan R. Hansford, Dong-Anh Khuong-Quang, Philippe Schucht, Theoni Maragkou, Tareq A. Juratli, Matthias Meinhardt, Sabrina Zechel, Christine Stadelmann, Roland Coras, Oliver W. Sakowitz, Benjamin Goeppert, Jens Schittenhelm, Nima Etminan, Miriam Ratliff, Christel Herold-Mende, Stefan M Pfister, Wolfgang Wick, Sandro M. Krieg, Andreas von Deimling, Felix Sahm, and Luca Bertero |
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| 245 | 1 | 0 | |a Distinct molecular profile and outcome of oligodendroglioma, IDH-mutant, 1p/19q-codeleted, and TERTp-wildtype |b a grade 1 oligodendroglioma of young patients? |c Filippo Nozzoli, Ramin Rahmanzade, Simone Schmid, Leonille Schweizer, Daniel Schrimpf, Dennis Friedel, Kirsten Göbel, David E. Reuss, Rouzbeh Banan, Philipp Sievers, Stefan Pusch, Henri Bogumil, Felix Hinz, Abigail K. Suwala, Fuat Kaan Aras, Lukas Friedrich, Simona Osella-Abate, Alessia Andrea Ricci, Alessandra Macciotta, Thorsten Simon, Gudrun Fleischhack, Kathy Keyvani, Jordan R. Hansford, Dong-Anh Khuong-Quang, Philippe Schucht, Theoni Maragkou, Tareq A. Juratli, Matthias Meinhardt, Sabrina Zechel, Christine Stadelmann, Roland Coras, Oliver W. Sakowitz, Benjamin Goeppert, Jens Schittenhelm, Nima Etminan, Miriam Ratliff, Christel Herold-Mende, Stefan M Pfister, Wolfgang Wick, Sandro M. Krieg, Andreas von Deimling, Felix Sahm, and Luca Bertero |
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| 520 | |a 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.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).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).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. | ||
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