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@ARTICLE{Schmid:296129,
author = {S. Schmid$^*$ and K. Mirchia and A. Tietze and I. Liu and
C. Siewert and J. Nückles and J. Schittenhelm and F.
Behling and M. Snuderl and C. Hartmann and S. Brandner and
S. M. L. Paine and A. Korshunov$^*$ and M. Hasselblatt and
R. Coras and S. Epari and C. Stadelmann and S. Zechel and M.
Simon and Y. Wilson and F. Gianno and G. L. Calixto-Hope and
V. Zherebitskiy and V. B. Kaimaktchiev and L. Robinson and
K. Aldape and E. W. Hoving and B. B. J. Tops and A. A.
Perera$^*$ and P. Göller and P. Hernáiz Driever and P.
Wesseling and A. Koch and A. Perry and F. Sahm$^*$ and D.
Jones$^*$ and D. Capper$^*$},
title = {{VGLL}-fusions define a new class of intraparenchymal {CNS}
schwannoma.},
journal = {Neuro-Oncology},
volume = {27},
number = {4},
issn = {1522-8517},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2025-00059},
pages = {1031-1045},
year = {2025},
note = {2025 May 15;27(4):1031-1045},
abstract = {Intracerebral schwannomas are rare tumors resembling their
peripheral nerve sheath counterparts but localized in the
CNS. They are not classified as a separate tumor type in the
2021 WHO classification. This study aimed to compile and
characterize these rare neoplasms morphologically and
molecularly.We analyzed 20 tumor samples by histology, RNA
Next-Generation Sequencing, DNA-methylation profiling, copy
number analyses, and single nucleus RNA sequencing
(snRNA-seq). Clinical data, including age, sex, and disease
progression, were collected. MRI series were included when
available.All cases with tissue available for histology
review (n=13) were morphologically consistent with
intracerebral schwannoma, but differed in their extent of
GFAP staining. All (n=20) shared DNA-methylation profiles
distinct from other CNS tumors, as well as from VGLL-altered
peripheral nerve sheath tumors. Most cases (n=14/17)
harbored fusions of either VGLL3 or VGLL1 (CHD7::VGLL3
(n=9/17) and EWSR1::VGLL1 (n=5/17)). In two cases the
presence of a VGLL3 fusion was also confirmed by CNA
analyses (n=2/17). MRI (n=4) showed well-defined, nodular
tumors with strong, homogeneous enhancement and no diffusion
restriction. Tumors were located throughout the neuroaxis
[supratentorial (n=15), infratentorial (n=4), and spinal
(n=1)]. snRNA-seq of a VGLL1-fused tumor indicated VGLL1
upregulation in $28.6\%$ of tumor cells (n=1). During median
follow-up of 1.8 years (range 3 months-9 years), none of the
tumors recurred (n=10).We identify and define a new benign
tumor class, designated VGLL-altered intraparenchymal CNS
schwannomas. These tumors feature VGLL alterations and a
specific DNA-methylation profile, with schwannoma-like
histopathology and CNS localization, akin to previously
classified intracerebral schwannomas.},
keywords = {VGLL (Other) / gliofibroma (Other) / glioma (Other) /
schwannoma (Other) / tumor (Other)},
cin = {B300 / HD01 / B360 / BE01},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B360-20160331 / I:(DE-He78)BE01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39713960},
doi = {10.1093/neuonc/noae269},
url = {https://inrepo02.dkfz.de/record/296129},
}