Crispr/Cas-based modeling of NF2 loss in meningioma cells

Background: Alterations of the neurofibromatosis type 2 gene (NF2) occur in more than fifty percent of sporadic meningiomas. Meningiomas develop frequently in the setting of the hereditary tumor syndrome NF2. Investigation of potential drug-based treatment options has been limited by the lack of appropriate in vitro and in vivo models. New methods: Using Crispr/Cas gene editing, of the malignant meningioma cell line IOMM-Lee, we generated a pair of cell clones characterized by either stable knockout of NF2 and loss of the protein product merlin or retained merlin protein (transfected control without gRNA). Results: IOMM-Lee cells lacking NF2 showed reduced apoptosis and formed bigger colonies compared to control IOMM-Lee cells. Treatment of non-transfected IOMM-Lee cells with the focal adhesion kinase (FAK) inhibitor GSK2256098 resulted in reduced colony sizes. Orthotopic mouse xenografts showed the formation of convexity tumors typical for meningiomas with NF2-depleted and control cells. Comparison with existing methods: No orthotopic meningioma models with genetically-engineered cell pairs are available so far. Conclusion: Our model based on Crispr/Cas-based gene editing provides paired meningioma cells suitable to study functional consequences and therapeutic accessibility of NF2/merlin loss.

Automated summary

Alterations of the NF2 gene are common in meningiomas, and this study used Crispr/Cas gene editing to create paired meningioma cells with or without NF2. NF2-deficient cells showed reduced apoptosis and larger colonies, and treatment with a FAK inhibitor decreased colony sizes, providing insights for potential therapeutic strategies. This novel model offers a valuable tool for studying the functional consequences and therapeutic approaches related to NF2/merlin loss in meningiomas.