Identification of Differential Epigenetic Landscape in NF2 and Non-NF2 Meningiomas

Meningiomas are the most frequently occurring primary intracranial tumours, with 70-80% of tumours classified as grade I or benign. In contrast, 5-20% tumours are grade II or atypical and 1-3% tumours are grade III or malignant. One major risk factor for the development of atypical meningioma is the inactivation of neurofibromin 2 (NF2) gene. Previous studies have highlighted the association of NF2 alteration-harbouring meningiomas, or NF2-meningiomas, with an increased clinical aggressiveness and higher risk of disease recurrence. Studies have also shown that a loss of H3K27me3 signature in meningiomas is associated with rapid progression and increased risk of recurrence. Our study investigates the changes in H3K27me3 signatures and differential H3K27me3 binding in NF2 meningiomas when compared to non-NF2 meningiomas using H3K27me3 ChIP-Seq data from NCBI GEO datasets. The data was analysed using Galaxy for differential binding analysis and motif finding was done using TOMTOM tool. Our findings suggest that NF2 mutations results in reduced chromatin silencing and potential transcriptional deregulation in comparison to non-NF2 meningiomas. This highlights the significance of H3K27me3 as an epigenetic marker in atypical meningiomas and set up the groundwork for investigating therapeutic strategies aimed at restoring epigenetic regulation in NF2-mutated tumours.