Rameen Beroukhim, MD, PhD; Ian Dunn, MD

Surgery is frequently insufficient for people with grade II–III meningioma tumors. For these people, no effective medical therapies exist. As part of a previous BSF funded study, this team examined several meningioma genomes, finding multiple genetic events, copy-number changes, and mutations with immediate clinical implications. Their study also showed that grade II and III tumors may be completely different diseases from grade I meningiomas. This project hypothesizes that genes found to be mutated in grade I meningiomas are also mutated in higher-grade meningiomas alongside mutations in additional genes. The team will perform whole-exome sequencing of 12 grade II and III meningiomas. They will then identify mutations affecting all genes in these tumors. Secondly, they willtest the hypothesis that high-grade meningiomas have higher rates of mutation, rearrangements, and copy-number changes genome-wide than grade I tumors. They will perform whole-genome sequencing of at least two grade II–III meningiomas, completely reconstructing these genomes, identifying all mutations and rearrangements both within and between genes. These studies will form a foundation for understanding why grade II–III meningiomas develop and could bring about potential therapeutic targets.