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

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 mol...

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Hauptverfasser: Sievers, Philipp (VerfasserIn) , Sill, Martin (VerfasserIn) , Blume, Christina (VerfasserIn) , Tauziede-Espariat, Arnault (VerfasserIn) , Schrimpf, Daniel (VerfasserIn) , Stichel, Damian (VerfasserIn) , Reuss, David (VerfasserIn) , Kardo, Helin (VerfasserIn) , Hartmann, Christian (VerfasserIn) , Mawrin, Christian (VerfasserIn) , Hasselblatt, Martin (VerfasserIn) , Stummer, Walter (VerfasserIn) , Schick, Uta (VerfasserIn) , Hench, Jürgen Christian Hans (VerfasserIn) , Frank, Stephan (VerfasserIn) , Ketter, Ralf (VerfasserIn) , Schweizer, Leonille (VerfasserIn) , Schittenhelm, Jens Florian (VerfasserIn) , Puget, Stéphanie (VerfasserIn) , Brandner, Sebastian (VerfasserIn) , Jaunmuktane, Zane (VerfasserIn) , Küsters, Benno (VerfasserIn) , Abdullaev, Zied (VerfasserIn) , Pekmezci, Melike (VerfasserIn) , Snuderl, Matija (VerfasserIn) , Ratliff, Miriam (VerfasserIn) , Herold-Mende, Christel (VerfasserIn) , Unterberg, Andreas (VerfasserIn) , Aldape, Kenneth (VerfasserIn) , Ellison, David W. (VerfasserIn) , Wesseling, Pieter (VerfasserIn) , Reifenberger, Guido (VerfasserIn) , Wick, Wolfgang (VerfasserIn) , Perry, Arie (VerfasserIn) , Varlet, Pascale (VerfasserIn) , Pfister, Stefan (VerfasserIn) , Jones, David T. W. (VerfasserIn) , Deimling, Andreas von (VerfasserIn) , Sahm, Felix (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2021
In: Acta neuropathologica
Year: 2021, Jahrgang: 141, Heft: 2, Pages: 281-290
ISSN:1432-0533
DOI:10.1007/s00401-020-02247-2
Online-Zugang:Resolving-System, kostenfrei: https://doi.org/10.1007/s00401-020-02247-2
Volltext
Verfasserangaben:Philipp Sievers, Martin Sill, Christina Blume, Arnault Tauziede-Espariat, Daniel Schrimpf, Damian Stichel, David E. Reuss, Helin Dogan, Christian Hartmann, Christian Mawrin, Martin Hasselblatt, Walter Stummer, Uta Schick, Jürgen Hench, Stephan Frank, Ralf Ketter, Leonille Schweizer, Jens Schittenhelm, Stéphanie Puget, Sebastian Brandner, Zane Jaunmuktane, Benno Küsters, Zied Abdullaev, Melike Pekmezci, Matija Snuderl, Miriam Ratliff, Christel Herold-Mende, Andreas Unterberg, Kenneth Aldape, David W. Ellison, Pieter Wesseling, Guido Reifenberger, Wolfgang Wick, Arie Perry, Pascale Varlet, Stefan M. Pfister, David T. W. Jones, Andreas von Deimling, Felix Sahm, The German Consortium “Aggressive Meningiomas”
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 05.07.2021
Published online: 14 December 2020
Beschreibung:Online Resource
ISSN:1432-0533
DOI:10.1007/s00401-020-02247-2

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