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Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

Oncogene volume 30, pages 2333–2344 (2011)Cite this article

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Abstract

Meningiomas are among the most common primary central nervous system tumours in adults. Studies focused on the molecular basis for meningioma development are hampered by a lack of information with regard to the cell of origin for these brain tumours. Herein, we identify a prostaglandin D synthase-positive meningeal precursor as the cell of origin for murine meningioma, and show that neurofibromatosis type 2 (Nf2) inactivation in prostaglandin D2 synthase (PGDS) (+) primordial meningeal cells, before the formation of the three meningeal layers, accounts for the heterogeneity of meningioma histological subtypes. Using a unique PGDSCre strain, we define a critical embryonic and early postnatal developmental window in which biallelic Nf2 inactivation in PGDS (+) progenitor cells results in meningioma formation. Moreover, we identify differentially expressed markers that characterize the two major histological meningioma subtypes both in human and mouse tumours. Collectively, these findings establish the cell of origin for these common brain tumours as well as a susceptible developmental period in which signature genetic mutations culminate in meningioma formation.

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Acknowledgements

We thank A Berns for p16Ink4a and p53flox mutant mice; S Dufour and JP Thiery for HtPACre mice; Y Urade for the PGDS genomic fragment; M Pla and staff of the Institut Universitaire d’Hematologie (IUH), Universite Paris 7, for mouse housing; N Karboul for technical assistance; and M Catala and W Van Furth for helpful discussions. This work was supported by Grants from the US Army Medical Research and Materiel Command (DAMD17-02-1-0645 to MG), James S McDonnell Foundation (to DHG and MG), Association Neurofibromatoses et Recklinghausen, the Vincent Buono Research Fund (to DHG and MG) and Inserm.

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  1. B Hegedus

    Present address: 8Current address: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria,

Authors and Affiliations

  1. Inserm, U674, Paris, France

    M Kalamarides, M Niwa-Kawakita, F Chareyre, E Taranchon, Z-Y Han, C Martinelli & M Giovannini

  2. Université Paris 7—Denis Diderot, Institut Universitaire d’Hématologie, Paris, France

    M Kalamarides, M Niwa-Kawakita, F Chareyre, E Taranchon, Z-Y Han, C Martinelli & M Giovannini

  3. AP-HP, Hôpital Beaujon, Service de Neurochirurgie, Clichy, France

    M Kalamarides

  4. Molecular Neuro-Oncology and Pathology Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    A O Stemmer-Rachamimov

  5. Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, USA

    E A Lusis

  6. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA

    B Hegedus & D H Gutmann

  7. Center for Neural Tumor Research, House Ear Institute, Los Angeles, CA, USA

    M Giovannini

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Correspondence to M Giovannini.

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Kalamarides, M., Stemmer-Rachamimov, A., Niwa-Kawakita, M. et al. Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes. Oncogene 30, 2333–2344 (2011). https://doi.org/10.1038/onc.2010.609

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