Journal Article

DKFZ-2025-01482

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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. (First author)DKFZ* ; Schmid, S.DKFZ* ; Schweizer, L.DKFZ* ; Schrimpf, D. ; Friedel, D. ; Göbel, K. ; Reuss, D. E.DKFZ* ; Banan, R.DKFZ* ; Sievers, P.DKFZ* ; Pusch, S.DKFZ* ; Bogumil, H.DKFZ* ; Hinz, F.DKFZ* ; Suwala, A. K.DKFZ* ; Aras, F. K.DKFZ* ; Friedrich, L.DKFZ* ; Osella-Abate, S. ; Ricci, A. A. ; Macciotta, A. ; Simon, T. ; Fleischhack, G. ; Keyvani, K. ; Hansford, J. R. ; Khuong-Quang, D.-A. ; Schucht, P. ; Maragkou, T. ; Juratli, T. A. ; Meinhardt, M. ; Zechel, S. ; Stadelmann, C. ; Coras, R. ; Sakowitz, O. W. ; Goeppert, B. ; Schittenhelm, J. ; Etminan, N. ; Ratliff, M. ; Herold-Mende, C. ; Pfister, S.DKFZ* ; Wick, W.DKFZ* ; Krieg, S. M. ; von Deimling, A.DKFZ* ; Sahm, F. (Last author)DKFZ* ; Bertero, L.

2025
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noaf141

Abstract: 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 tumour proliferation. Although there are a few reports on a TERTp-wildtype subset of these tumours in adolescents and young adults, the frequency, molecular characteristics and prognostic implications of TERTp-wildtype status in oligodendrogliomas remains elusive.We retrospectively analysed 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 (p<0.001), CNS WHO grade 2 (p=0.003), and the absence of additional DNA copy number variations (CNVs) beyond the pathognomonic 1p/19q codeletion (p<0.001). Epigenetic profiling demonstrated TERTp-wildtype tumours 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 favour TERT overexpression in TERTp-wildtype oligodendrogliomas. WES showed no TM-related genes alterations in TERTp-wildtype cases. Cox regression analysis confirmed TERTp-wildtype status as an independent prognostic factor for more favourable progression-free survival (PFS) (p=0.009).In conclusion, 'oligodendroglioma, IDH-mutant, 1p/19q-codeleted and TERTp-wildtype' represents a distinct molecular subgroup associated with younger age and a better clinical course compared to CNS WHO grade 2 oligodendrogliomas.

Keyword(s): TERT promoter ; adolescents and young adults ; methylation ; oligodendroglioma ; progression-free survival

Note: #EA:B300#LA:B300# /epub

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Contributing Institute(s):

1. KKE Neuropathologie (B300)
2. DKTK HD zentral (HD01)
3. DKTK Koordinierungsstelle Berlin (BE01)
4. DKTK Koordinierungsstelle Frankfurt (FM01)
5. B062 Pädiatrische Neuroonkologie (B062)
6. KKE Neuroonkologie (B320)

Research Program(s):

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

Appears in the scientific report 2025

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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