P18.04.B SINGLE CELL TRANSCRIPTOMIC ANALYSIS IDENTIFIES DISTINCT INTRATUMORAL SUBCLONES IN MENINGIOMA

Abstract

Abstract BACKGROUND Meningiomas arise from the leptomeninges of the brain and spinal cord. Despite being the most common intracranial tumor in adults, risk stratification remains challenging. Currently, tumors are graded based on histology as well as molecular markers. In recent years, several epigenomic classification systems with a correlation to patient outcome have been proposed for meningiomas. However, these classification systems do not discriminate between effects of the tumor microenvironment and the tumor itself or consider distinct intratumoral subpopulations with different phenotypes. To address this, we set out to investigate intratumoral differences and correlated them with gene expression differences. MATERIAL AND METHODS We applied single nuclei RNA sequencing (10X Genomics 3’) to 30 meningioma samples to obtain transcriptomic profiles on single cell level. Copy number variations were estimated for single cells based on the transcriptomic profiles to identify clonal differences within a given tumor. RESULTS Based on aberrations in the copy number profile, we were able to identify distinct subclones within the same tumor, which could in many cases be connected to a change in the transcriptomic profile of the respective subclone. Different patterns of subclonal diversity were observed between tumor grades. Further insight into the subpopulations was used to infer a novel model for prognostication which was validated by methylation data. CONCLUSION Altogether, these results demonstrate that diverse subclones co-exist within meningioma, especially within higher-grade tumors. Effects of meningioma subclones on tumor growth and their relevance for clinical risk prediction remain to be elucidated.