Identification of Genomic Alterations Underlying Non-NF2-related Initiation of Meningioma Tumorigenesis

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Dr. Michel Kalamarides, PhD

Meningiomas are common central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Around 50% of patients with Neurofibromatosis 2 (NF2) develop meningiomas. The NF2 gene is also involved in sporadic meningiomas: 60% show inactivation of this gene.

In a previous study funded by the BSF, Dr. Kalamarides analyzed the genetic mechanisms underlying tumor progression in meningiomas. He used a new powerful technology: the 500K Single Nucleotide Polymorphism array (500K SNP), the latest version gene mapping array. By comparison of the genomic differences between low grade and high grade meningiomas in the same patient, Dr. Kalamarides identified molecular mechanisms involved in tumor progression (paper under preparation). He showed that 2 major groups of meningiomas are clearly different, based on the NF2 gene status. However, the genetic initiation remains unclear in 40% of meningiomas without NF2 gene mutation.

In this present study, Dr. Kalamarides aims to identify candidate genes involved in meningioma tumorigenesis initiation. He will conduct a whole genome 500K SNP analysis on 40 benign meningiomas, 20 with normal NF2 protein and 20 with mutated NF2 protein. By comparison of their genomic differences (and control blood), Dr. Kalamarides will be able to identify candidate genes that are independent of NF2 and involved in tumor initiation.

Ultimately, the identification of these putative genes will lead to better understanding of the molecular mechanisms underlying non-NF2 related meningioma tumorigenesis (40% of meningiomas), to generate additional animal models and to identify new potential therapeutic targets.