Related Experiment Video
Updated: May 17, 2026
Identifying, Diagnosing, and Grading Malignant Peripheral Nerve Sheath Tumors in Genetically Engineered Mouse Models
Published on: May 17, 2024
Meningioma progression in mice triggered by Nf2 and Cdkn2ab inactivation
M Peyre1, A Stemmer-Rachamimov, E Clermont-Taranchon
1Department of Neurosurgery, AP-HP, Hopital Beaujon, Clichy, France.
Abstract:
Aggressive variants of meningiomas (WHO grade II and III) represent up to 30% of those tumors that are among the most common primary central nervous system tumors in adults. Currently, there is no effective treatment for grade-II and -III meningiomas, the main treatment remaining surgical excision. Genetic studies have highlighted two main events associated with meningioma progression: an increase of chromosomal instability in tumors with NF2 inactivation and homozygous deletions or point mutations of the CDKN2AB locus. In this study we demonstrated that in mice, in addition to bi-allelic Nf2 inactivation, homozygous and heterozygous Adenovirus Cre-mediated Cdkn2ab deletions lead to increased meningioma frequency (72% and 50%, respectively) with a shorter latency (3.5 and 7.8 months, respectively) compared with control cohorts and induce grade II/III meningioma progression with an incidence of 34% and 28%, respectively. Moreover, Cdkn2ab inactivation in arachnoidal cells was associated with decreased senescence compared with Nf2(-/-) and wild-type arachnoidal cells in vitro. We have established three mouse meningioma cell lines and generated a syngenic orthotopic meningioma mouse model with 50-100% grade-II/III meningiomas after reimplantation. Comparative genomic hybridization of four meningiomas from Cdkn2ab homozygous mice and three cell cultures revealed the absence of unbalanced chromosomal segments in tumors and several chromosome imbalances in cell cultures. In addition, we were able to detect meningiomas by using bioluminescence and to evaluate tumor vascular permeability by dynamic magnetic resonance imaging. These results show that Nf2 and Cdkn2ab cooperate to promote meningioma progression in mice. The short latency of tumor development and the ability to derive grade II/III meningioma cell cultures are key aspects of this model to promote its use in pre-clinical drug testing.
Insights
Genetic factors NF2 and CDKN2AB cooperate to drive aggressive meningioma tumor growth in mice. This study establishes a new preclinical model for testing drugs against these challenging brain tumors.
Area of Science:
- Neuro-oncology
- Cancer Genetics
- Tumor Progression
Background:
- Aggressive meningiomas (WHO grade II and III) are common primary central nervous system tumors with no effective treatments beyond surgery.
- Tumor progression is linked to chromosomal instability, NF2 inactivation, and CDKN2AB locus alterations.
Purpose of the Study:
- To investigate the cooperative role of NF2 and CDKN2AB in meningioma development and progression using a mouse model.
- To establish a preclinical model for evaluating potential therapeutic interventions for aggressive meningiomas.
Main Methods:
- Adenovirus Cre-mediated deletion of Nf2 and Cdkn2ab in mice.
- Establishment of mouse meningioma cell lines and a syngenic orthotopic model.
- In vitro senescence assays, comparative genomic hybridization, bioluminescence imaging, and dynamic MRI for tumor assessment.
Main Results:
- Bi-allelic Nf2 inactivation combined with Cdkn2ab deletion significantly increased meningioma frequency and accelerated tumor progression in mice.
- Cdkn2ab inactivation reduced senescence in arachnoidal cells.
- The developed mouse model consistently produced grade II/III meningiomas and allowed for in vivo tumor detection and vascular permeability evaluation.
Conclusions:
- NF2 and CDKN2AB genetically cooperate to promote meningioma progression in mice.
- This novel mouse model offers a valuable platform for preclinical drug testing in aggressive meningiomas due to its short latency and ability to generate high-grade tumors.
