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@ARTICLE{Nozzoli:303035,
author = {F. Nozzoli and R. Rahmanzade$^*$ and S. Schmid$^*$ and L.
Schweizer$^*$ and D. Schrimpf and D. Friedel and K. Göbel
and D. E. Reuss$^*$ and R. Banan$^*$ and P. Sievers$^*$ and
S. Pusch$^*$ and H. Bogumil$^*$ and F. Hinz$^*$ and A. K.
Suwala$^*$ and F. K. Aras$^*$ and L. Friedrich$^*$ and S.
Osella-Abate and A. A. Ricci and A. Macciotta and T. Simon
and G. Fleischhack and K. Keyvani and J. R. Hansford and
D.-A. Khuong-Quang and P. Schucht and T. Maragkou and T. A.
Juratli and M. Meinhardt and S. Zechel and C. Stadelmann and
R. Coras and O. W. Sakowitz and B. Goeppert and J.
Schittenhelm and N. Etminan and M. Ratliff and C.
Herold-Mende and S. Pfister$^*$ and W. Wick$^*$ and S. M.
Krieg and A. von Deimling$^*$ and F. Sahm$^*$ and L.
Bertero},
title = {{D}istinct molecular profile and outcome of
oligodendroglioma, {IDH}-mutant, 1p/19q-codeleted and
{TERT}p-wildtype: a grade 1 oligodendroglioma of young
patients?},
journal = {Neuro-Oncology},
volume = {nn},
issn = {1522-8517},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2025-01482},
pages = {nn},
year = {2025},
note = {#EA:B300#LA:B300# /epub},
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.},
keywords = {TERT promoter (Other) / adolescents and young adults
(Other) / methylation (Other) / oligodendroglioma (Other) /
progression-free survival (Other)},
cin = {B300 / HD01 / BE01 / FM01 / B062 / B320},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)BE01-20160331 / I:(DE-He78)FM01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B320-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40692489},
doi = {10.1093/neuonc/noaf141},
url = {https://inrepo02.dkfz.de/record/303035},
}