Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1

Autor: Matija Snuderl, Zied Abdullaev, Christel Herold-Mende, Ralf Ketter, Uta Schick, Zane Jaunmuktane, David T.W. Jones, Christian Mawrin, Daniel Schrimpf, Leonille Schweizer, Christina Blume, Miriam Ratliff, Arnault Tauziède-Espariat, Pascale Varlet, Arie Perry, Felix Sahm, Damian Stichel, Walter Stummer, Martin Hasselblatt, Jürgen Hench, Stefan M. Pfister, Pieter Wesseling, Guido Reifenberger, Jens Schittenhelm, Helin Dogan, Andreas von Deimling, David W. Ellison, Christian Hartmann, Philipp Sievers, Melike Pekmezci, Wolfgang Wick, David E. Reuss, Stephan Frank, Martin Sill, Sebastian Brandner, Stéphanie Puget, Benno Küsters, Kenneth Aldape, Andreas Unterberg
Přispěvatelé: CCA - Imaging and biomarkers, CCA - Cancer biology and immunology, Pathology
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Acta Neuropathologica, 141, 281-290
Acta Neuropathologica, 141, 2, pp. 281-290
Sievers, P, Sill, M, Blume, C, Tauziede-Espariat, A, Schrimpf, D, Stichel, D, Reuss, D E, Dogan, H, Hartmann, C, Mawrin, C, Hasselblatt, M, Stummer, W, Schick, U, Hench, J, Frank, S, Ketter, R, Schweizer, L, Schittenhelm, J, Puget, S, Brandner, S, Jaunmuktane, Z, Küsters, B, Abdullaev, Z, Pekmezci, M, Snuderl, M, Ratliff, M, Herold-Mende, C, Unterberg, A, Aldape, K, Ellison, D W, Wesseling, P, Reifenberger, G, Wick, W, Perry, A, Varlet, P, Pfister, S M, Jones, D T W, von Deimling, A, Sahm, F & The German Consortium “Aggressive Meningiomas” 2021, ' Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1 ', Acta Neuropathologica, vol. 141, no. 2, pp. 281-290 . https://doi.org/10.1007/s00401-020-02247-2
Acta Neuropathologica, 141(2), 281-290. Springer Verlag
Acta Neuropathologica
ISSN: 0001-6322
DOI: 10.1007/s00401-020-02247-2
Popis: Clear cell meningioma represents an uncommon variant of meningioma that typically affects children and young adults. Although an enrichment of loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset of tumors (n = 31), initially identified through genome-wide DNA methylation screening among a cohort of 3093 meningiomas, of which most were diagnosed histologically as clear cell meningioma. This cohort was further supplemented by an additional 11 histologically diagnosed clear cell meningiomas for analysis (n = 42). Targeted DNA sequencing revealed SMARCE1 mutations in 33/34 analyzed samples, accompanied by a nuclear loss of expression determined via immunohistochemistry and a decreased SMARCE1 transcript expression in the tumor cells. Analysis of time to progression or recurrence of patients within the clear cell meningioma group (n = 14) in comparison to those with meningioma WHO grade 2 (n = 220) revealed a similar outcome and support the assignment of WHO grade 2 to these tumors. Our findings indicate the existence of a highly distinct epigenetic signature of clear cell meningiomas, separate from all other variants of meningiomas, with recurrent mutations in the SMARCE1 gene. This suggests that these tumors may arise from a different precursor cell population than the broad spectrum of the other meningioma subtypes.
Databáze: OpenAIRE
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