Natural history of meningioma development in mice reveals: A synergy of Nf2 and p16Ink4a mutations

Michel Kalamarides, Anat O. Stemmer-Rachamimov, Masaya Takahashi, Zhi Yan Han, Fabrice Chareyre, Michiko Niwa-Kawakita, Peter M. Black, Rona S. Carroll, Marco Giovannini

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Meningiomas account for approximately 30% of all primary central nervous system tumors and are found in half of neurofibromatosis type 2 patients often causing significant morbidity. Although most meningiomas are benign, 10% are classified as atypical or anaplastic, displaying aggressive clinical behavior. Biallelic inactivation of the neurofibromatosis 2 (NF2) tumor suppressor is associated with meningioma formation in all NF2 patients and 60% of sporadic meningiomas. Deletion of the p16INK4a/p14ARF locus is found in both benign and malignant meningiomas, while mutation of the p53 tumor suppressor gene is uncommon. Previously, we inactivated Nf2 in homozygous conditional knockout mice by adenoviral Cre delivery and showed that Nf2 loss in arachnoid cells is rate-limiting for meningioma formation. Here, we report that additional nullizygosity for p16Ink4a increases the frequency of meningioma and meningothelial proliferation in these mice without modifying the tumor grade. In addition, by using magnetic resonance imaging (MRI) to screen a large cohort of mutant mice, we were able to detect meningothelial proliferation and meningioma development opening the way to future studies in which therapeutic interventions can be tested as preclinical assessment of their potential clinical application.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
JournalBrain Pathology
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

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    Kalamarides, M., Stemmer-Rachamimov, A. O., Takahashi, M., Han, Z. Y., Chareyre, F., Niwa-Kawakita, M., Black, P. M., Carroll, R. S., & Giovannini, M. (2008). Natural history of meningioma development in mice reveals: A synergy of Nf2 and p16Ink4a mutations. Brain Pathology, 18(1), 62-70. https://doi.org/10.1111/j.1750-3639.2007.00105.x