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Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations.

Paper Id
Reuss DE,Piro RM,Jones DT,Simon M,Ketter R,Kool M,Becker A,Sahm F,Pusch S,Meyer J,Hagenlocher C,Schweizer L,Capper D,Kickingereder P,Mucha J,Koelsche C,Jäger N,Santarius T,Tarpey PS,Stephens PJ,Andrew Futreal P,Wellenreuther R,Kraus J,Lenartz D,Herold-Mende C,Hartmann C,Mawrin C,Giese N,Eils R,Collins VP,König R,Wiestler OD,Pfister SM and von Deimling A
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Acta neuropathologica 2013;125(3):351-8
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.
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Genes Analysed
Mutated Samples
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Genes Samples CDS Mutation AA Mutation
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Non-Mutant Genes Gene Id (COSG)
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Non-Mutant Samples Sample Id (COSS)
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Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq FATHMM-MKL
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Sample Gene Expression Expr Level (Z-Score)

Over Expressed; Z-Score > 2.0

Under Expressed; Z-Score < -2.0

Normal; Z-Score within the range -2.0 to 2.0

CN Type Minor Allele Copy Number CN Segment Posn. Average Ploidy

1. N/A represents cases where the average ploidy value is not available( mostly ICGC samples). For some TCGA samples where the minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, the ASCAT algorithm was used to calculate the average ploidy.

3. For CGP samples, the PICNIC algorithm was used to calculate the average ploidy.

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Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type