EPCO-29. GENOMIC PROFILING OF SPORADIC MULTIPLE MENINGIOMAS

Abstract

Abstract INTRODUCTION In rare cases, sporadic meningiomas can occur as multiple tumors in the same patient without a known germline mutation. While the underlying mechanism that leads to the formation of these multiple lesions has been hypothesized to be monoclonal or independent, the genomic profiles to support these theories remain understudied. METHODS Patients with an absence of family history of meningioma and prior radiation history with multiple metachronous meningiomas were included. All tissue underwent whole exome sequencing and analysis of somatic single nucleotide variations (SNV), small insertion/deletion (INDEL) events together with copy number variations (CNV) was performed. The genomic findings were correlated with clinical data. RESULTS A cohort of 13 meningiomas and one dural specimen, from five individuals was studied. The majority (9/13 tumors) of tumors had NF2 mutation/Chr22 loss. Four out of 5 cases had a monoclonal origination, whereas one case displayed an independent clonal formation. The somatic profile of dura was unrevealing. In contrast to the current understanding, we found monoclonal formation of multiple meningiomas is not exclusive to NF2 driven cases, as non-NF2 mutated meningiomas can too display a monoclonal etiology. Moreover, multiple monoclonal-originating lesions did not always display a homogenous profile, but rather exhibited heterogeneity through branching evolution, where some lesions acquired genomic alterations associated with aggressive behavior. The histological characterization of multiple meningioma cases does not necessarily overlap with the genomic clustering. CONCLUSION To our knowledge, this is the first study to use unbiased comprehensive genomic methods to reveal the heterogeneity of multiple meningioma genomic profiles. Our extensive genomic characterization of this cohort revealed that monoclonal formation can be observed both in NF2 and non-NF2 mutant meningiomas and can introduce heterogeneity. Therefore, in order to understand the full scope of each individual’s disease, detailed genomic profiling of all lesions, when possible, should be performed.