Journal Article

DKFZ-2025-00059

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Schmid, S.DKFZ* ; Mirchia, K. ; Tietze, A. ; Liu, I. ; Siewert, C. ; Nückles, J. ; Schittenhelm, J. ; Behling, F. ; Snuderl, M. ; Hartmann, C. ; Brandner, S. ; Paine, S. M. L. ; Korshunov, A.DKFZ* ; Hasselblatt, M. ; Coras, R. ; Epari, S. ; Stadelmann, C. ; Zechel, S. ; Simon, M. ; Wilson, Y. ; Gianno, F. ; Calixto-Hope, G. L. ; Zherebitskiy, V. ; Kaimaktchiev, V. B. ; Robinson, L. ; Aldape, K. ; Hoving, E. W. ; Tops, B. B. J. ; Perera, A. A.DKFZ* ; Göller, P. ; Hernáiz Driever, P. ; Wesseling, P. ; Koch, A. ; Perry, A. ; Sahm, F.DKFZ* ; Jones, D.DKFZ* ; Capper, D.DKFZ*

2025
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noae269

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.

Keyword(s): VGLL ; gliofibroma ; glioma ; schwannoma ; tumor

Note: 2025 May 15;27(4):1031-1045

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Contributing Institute(s):

1. KKE Neuropathologie (B300)
2. DKTK HD zentral (HD01)
3. Pädiatrische Gliomforschung (B360)
4. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

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

Appears in the scientific report 2024

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

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