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@ARTICLE{Guidara:291389,
author = {S. Guidara and A. Seyve and D. Poncet and C. Leonce and
P.-P. Bringuier and A. McLeer and D. Sturm$^*$ and S.
Cartalat and T. Picart and A. Ferrari and J. Hench and S.
Frank and D. Meyronet and F. Ducray and M. Barritault},
title = {{C}haracteristics of {H}3{K}27{M}-mutant diffuse gliomas
with a non-midline location.},
journal = {Journal of neuro-oncology},
volume = {169},
number = {2},
issn = {0167-594X},
address = {Dordrecht [u.a.]},
publisher = {Springer Science + Business Media B.V},
reportid = {DKFZ-2024-01377},
pages = {391-398},
year = {2024},
note = {2024 Sep;169(2):391-398},
abstract = {Diffuse midline gliomas (DMG) with H3K27 alterations
(H3K27M-DMG) are a highly aggressive form of brain cancer.
In rare cases, H3K27 mutations have been observed in diffuse
non-midline gliomas (DNMG). It is currently unclear how
these tumors should be classified. Herein, we analyze the
characteristics of DNMG with H3K27M mutations.We reviewed
the clinical, radiological and histological characteristics
of all patients with an H3K27M mutated diffuse glioma
diagnosed in our institution, between 2016 and 2023, to
identify cases with a non-midline location. We then
performed a molecular characterization (DNA methylation
profiling, whole genome and transcriptome sequencing or
targeted sequencing) of patients with an H3K27M-mutant DNMG
and reviewed previously reported cases.Among 51 patients (18
children and 33 adults) diagnosed with an H3K27M diffuse
glioma, we identified two patients $(4\%)$ who had a
non-midline location. Including our two patients, 39
patients were reported in the literature with an
H3K27M-mutant DNMG. Tumors were most frequently located in
the temporal lobe $(48\%),$ affected adolescents and adults,
and were associated with a poor outcome (median overall
survival was 10.3 months (0.1-84)). Median age at diagnosis
was 19.1 years. Tumors frequently harbored TP53 mutations
$(74\%),$ ATRX mutations $(71\%)$ and PDGFRA mutations or
amplifications $(44\%).$ In DNA methylation analysis,
H3K27M-mutant DNMG clustered within or close to the
reference group of H3K27M-mutant DMG. Compared to their
midline counterpart, non-midline gliomas with H3K27M
mutations seemed more frequently associated with PDGFRA
alterations.DNMG with H3K27M mutations share many
similarities with their midline counterpart, suggesting that
they correspond to a rare anatomical presentation of these
tumors. This is of paramount importance, as they may benefit
from new therapeutic approaches such as ONC201.},
keywords = {Diffuse intrinsic pontine glioma (Other) / Diffuse midline
glioma H3 K27-altered (Other) / H3K27M (Other) / H3K28M
(Other) / Methylation (Other) / Non-midline (Other) /
Pediatric glioma (Other)},
cin = {B360 / HD01},
ddc = {610},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38937309},
doi = {10.1007/s11060-024-04733-z},
url = {https://inrepo02.dkfz.de/record/291389},
}