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YAP1-fusions in pediatric NF2-wildtype meningioma

  • Philipp Sievers
  • Jason Chiang
  • Daniel Schrimpf
  • Damian Stichel
  • Nagarajan Paramasivam
  • Martin Sill
  • Tenzin Gayden
  • Belen Casalini
  • David E. Reuss
  • James Dalton
  • Kristian W. Pajtler
  • Daniel Hänggi
  • Christel Herold-Mende
  • Elisabeth Rushing
  • Andrey Korshunov
  • Christian Mawrin
  • Michael Weller
  • Matthias Schlesner
  • Wolfgang Wick
  • Nada Jabado
  • David T. W. Jones
  • Stefan M. Pfister
  • Andreas von Deimling
  • David W. Ellison
  • Felix SahmEmail author
Correspondence

Meningioma is the most common primary central nervous system (CNS) tumor [8]. In contrast to adulthood, meningiomas are rare among children and adolescents and frequently (about 38%) occur in the context of tumor predisposition syndromes [12]. In line with the frequent inactivation of NF2 in adult meningiomas, neurofibromatosis type 2 is the most common inherited syndrome predisposing to the early development of meningiomas, which are often multiple. Other germline alterations predisposing to meningioma development are SMARCE1 [14] and SUFU mutations [1]. More recently identified drivers of meningiomas include AKT1/TRAF7, SMO, KLF4/TRAF7, and PIK3CA mutations [3, 5].

The mutational underpinnings of sporadic pediatric meningioma have remained elusive to date. We report in-frame gene rearrangements predicted to result in fusions involving YAP1 in nine meningiomas. We initially identified a YAP1-MAML2fusion by clinical RNA sequencing in a 4-year-old female patient with an...

Notes

Acknowledgements

We thank L. Dörner and H. Y. Nguyen for skillful technical assistance and the microarray unit of the DKFZ Genomics and Proteomics Core Facility for providing Illumina DNA methylation array-related services. This study was supported by the German Cancer Aid (70112956) and Else Kröner-Fresenius Stiftung (EKFS 2015_A60). FS is a fellow of the Else Kröner Excellence Program of the Else Kröner-Fresenius Stiftung (EKFS 2017_EKES.24).

Supplementary material

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Supplementary file1 (PDF 53739 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Philipp Sievers
    • 1
    • 2
  • Jason Chiang
    • 3
  • Daniel Schrimpf
    • 1
    • 2
  • Damian Stichel
    • 1
    • 2
  • Nagarajan Paramasivam
    • 4
  • Martin Sill
    • 5
    • 6
  • Tenzin Gayden
    • 7
    • 8
    • 9
  • Belen Casalini
    • 1
    • 2
  • David E. Reuss
    • 1
    • 2
  • James Dalton
    • 3
  • Kristian W. Pajtler
    • 5
    • 6
    • 10
  • Daniel Hänggi
    • 11
  • Christel Herold-Mende
    • 12
  • Elisabeth Rushing
    • 13
  • Andrey Korshunov
    • 1
    • 2
    • 5
  • Christian Mawrin
    • 14
  • Michael Weller
    • 15
  • Matthias Schlesner
    • 4
  • Wolfgang Wick
    • 16
    • 17
  • Nada Jabado
    • 7
    • 8
    • 9
  • David T. W. Jones
    • 5
    • 18
  • Stefan M. Pfister
    • 5
    • 6
    • 10
  • Andreas von Deimling
    • 1
    • 2
  • David W. Ellison
    • 3
  • Felix Sahm
    • 1
    • 2
    • 5
    Email author
  1. 1.Department of Neuropathology, Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK)German Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department of PathologySt. Jude Children’s Research HospitalMemphisUSA
  4. 4.Bioinformatics and Omics Data AnalyticsGerman Cancer Research Center (DKFZ)HeidelbergGermany
  5. 5.Hopp Children’s Cancer Center Heidelberg (KiTZ)HeidelbergGermany
  6. 6.Division of Pediatric Neurooncology, German Cancer Consortium (DKTK)German Cancer Research Center (DKFZ)HeidelbergGermany
  7. 7.Department of Human GeneticsMcGill UniversityMontrealCanada
  8. 8.Department of PediatricsMcGill UniversityMontrealCanada
  9. 9.The Research Institute of the McGill University Health CenterMontrealCanada
  10. 10.Department of Pediatric Oncology, Hematology, Immunology and PulmonologyUniversity Hospital HeidelbergHeidelbergGermany
  11. 11.Department of Neurosurgery, University Medical Centre MannheimUniversity of HeidelbergMannheimGermany
  12. 12.Division of Experimental Neurosurgery, Department of NeurosurgeryUniversity Hospital HeidelbergHeidelbergGermany
  13. 13.Institute of NeuropathologyUniversity Hospital and University of ZurichZurichSwitzerland
  14. 14.Institute of NeuropathologyOtto-von-Guericke UniversityMagdeburgGermany
  15. 15.Department of NeurologyUniversity Hospital and University of ZurichZurichSwitzerland
  16. 16.Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK)German Cancer Research Center (DKFZ)HeidelbergGermany
  17. 17.Department of Neurology and Neurooncology Program, National Center for Tumor DiseasesHeidelberg University HospitalHeidelbergGermany
  18. 18.Pediatric Glioma Research GroupGerman Cancer Research Center (DKFZ)HeidelbergGermany

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