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Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations

Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expression of a distinct pattern of cytokeratins and clinically by pronounced perifocal brain e...

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Main Authors: Reuss, David (Author) , Piro, Rosario M. (Author) , Jones, David T. W. (Author) , Simon, Matthias (Author) , Ketter, Ralf (Author) , Kool, Marcel (Author) , Becker, Albert (Author) , Sahm, Felix (Author) , Pusch, Stefan (Author) , Meyer, Jochen (Author) , Hagenlocher, Christian (Author) , Schweizer, Leonille (Author) , Capper, David (Author) , Vollmuth, Philipp (Author) , Mucha, Jana (Author) , Kölsche, Christian (Author) , Jäger, Natalie (Author) , Santarius, Thomas (Author) , Tarpey, Patrick S. (Author) , Stephens, Philip J. (Author) , Futreal, P. Andrew (Author) , Wellenreuther, Ruth (Author) , Kraus, Jürgen (Author) , Lenartz, Doris (Author) , Herold-Mende, Christel (Author) , Hartmann, Christian (Author) , Mawrin, Christian (Author) , Giese, Nathalia (Author) , Eils, Roland (Author) , Collins, V. Peter (Author) , König, Rainer (Author) , Wiestler, Otmar D. (Author) , Pfister, Stefan (Author) , Deimling, Andreas von (Author)
Format: Article (Journal)
Language:English
Published: 12 February 2013
In: Acta neuropathologica
Year: 2013, Volume: 125, Issue: 3, Pages: 351-358
ISSN:1432-0533
DOI:10.1007/s00401-013-1093-x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s00401-013-1093-x
Verlag, lizenzpflichtig, Volltext: https://link.springer.com/article/10.1007%2Fs00401-013-1093-x
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Author Notes:David E. Reuss, Rosario M. Piro, David T.W. Jones, Matthias Simon, Ralf Ketter, Marcel Kool, Albert Becker, Felix Sahm, Stefan Pusch, Jochen Meyer, Christian Hagenlocher, Leonille Schweizer, David Capper, Phillipp Kickingereder, Jana Mucha, Christian Koelsche, Natalie Jäger, Thomas Santarius, Patrick S. Tarpey, Philip J. Stephens, P. Andrew Futreal, Ruth Wellenreuther, Jürgen Kraus, Doris Lenartz, Christel Herold-Mende, Christian Hartmann, Christian Mawrin, Nathalia Giese, Roland Eils, V. Peter Collins, Rainer König, Otmar D. Wiestler, Stefan M. Pfister, Andreas von Deimling
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Summary:Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expression of a distinct pattern of cytokeratins and clinically by pronounced perifocal brain edema. Here we describe whole-exome sequencing analysis of DNA from 16 secretory meningiomas and corresponding constitutional tissues. All secretory meningiomas invariably harbored a mutation in both KLF4 and TRAF7. Validation in an independent cohort of 14 secretory meningiomas by Sanger sequencing or derived cleaved amplified polymorphic sequence (dCAPS) assay detected the same pattern, with KLF4 mutations observed in a total of 30/30 and TRAF7 mutations in 29/30 of these tumors. All KLF4 mutations were identical, affected codon 409 and resulted in a lysine to glutamine exchange (K409Q). KLF4 mutations were not found in 89 non-secretory meningiomas, 267 other intracranial tumors including gliomas, glioneuronal tumors, pituitary adenomas and metastases, 59 peripheral nerve sheath tumors and 52 pancreatic tumors. TRAF7 mutations were restricted to the WD40 domains. While KLF4 mutations were exclusively seen in secretory meningiomas, TRAF7 mutations were also observed in 7/89 (8 %) of non-secretory meningiomas. KLF4 and TRAF7 mutations were mutually exclusive with NF2 mutations. In conclusion, our findings suggest an essential contribution of combined KLF4 K409Q and TRAF7 mutations in the genesis of secretory meningioma and demonstrate a role for TRAF7 alterations in other non-NF2 meningiomas.
Item Description:Gesehen am 04.01.2022
Physical Description:Online Resource
ISSN:1432-0533
DOI:10.1007/s00401-013-1093-x

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