OS13 - 175 Genetic Profiling of Radiation Induced Meningiomas

Abstract

One-third of all primary central nervous system tumors in adults are meningiomas, which arise from the meninges. Although the majority of meningioma cases are not associated with an environmental risk factor, it is well established that individuals receiving radiation treatment to the CNS are susceptible to radiation-induced meningiomas (RIMs). The genomic integrity of spontaneous meningiomas has been extensively profiled by whole genome sequencing and exome sequencing, providing a well-developed catalogue of meningioma associated mutations. In contrast, a comprehensive understanding of the molecular changes associated with RIMs is not available. Comparative genomic hybridization (CGH) has previously revealed that >90% of RIMs possess multiple regions of DNA copy number alterations, with the most common chromosomal loss being chromosome 1p and 22q. These CGH based studies of gross chromosomal alterations suggest that radiation induced meningiomas show no significant differences to spontaneous meningiomas. We have extensively characterized RIMs through the profiling of their global CpG methylation, gene expression and mutation signatures. The integration of these three platforms at base-pair resolution methylation has facilitated the identification of molecular changes that contribute to RIM. This is the largest cohort of profiled meningiomas to date, providing a robust characterization of unique RIM features that can be exploited for future therapies.