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@ARTICLE{Muench:283138,
author = {A. Muench and D. Teichmann and D. Spille and P. Kuzman and
E. Perez and S.-A. May and W. C. Mueller and T. Kombos and
S. Nazari-Dehkordi and J. Onken and P. Vajkoczy and G.
Ntoulias and C. Bettencourt and A. von Deimling$^*$ and W.
Paulus and F. L. Heppner$^*$ and A. Koch$^*$ and D.
Capper$^*$ and D. Kaul and C. Thomas and L. Schweizer$^*$},
title = {{A} {N}ovel {T}ype of {IDH} {W}ild-type {G}lioma
{C}haracterized by {G}liomatosis {C}erebri-like {G}rowth
{P}attern, {TERT} {P}romoter {M}utation, and {D}istinct
{E}pigenetic {P}rofile.},
journal = {The American journal of surgical pathology},
volume = {47},
number = {12},
issn = {0147-5185},
address = {[Erscheinungsort nicht ermittelbar]},
publisher = {Ovid},
reportid = {DKFZ-2023-01925},
pages = {1364-1375},
year = {2023},
note = {2023 Dec 1;47(12):1364-1375},
abstract = {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.},
cin = {BE01 / FM01 / B300},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331 / I:(DE-He78)FM01-20160331 /
I:(DE-He78)B300-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37737691},
doi = {10.1097/PAS.0000000000002118},
url = {https://inrepo02.dkfz.de/record/283138},
}