Chromosome Instability and Transcriptomic Subpopulations Underlie Intratumor Heterogeneity in Meningioma

Meningiomas are the most common primary intracranial tumor, and high grade meningiomas are resistant to most cancer therapies. As intratumor heterogeneity is a driver of cancer resistance, we hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and shed light on tumor evolution. Thus, we performed multiplatform molecular profiling of 86 spatially distinct samples from 13 meningiomas to discover that alterations in chromosome structure underlie evolution of synchronous tumor subpopulations in high grade meningiomas. To understand the impact of genomic instability on gene expression in meningioma, we used single nucleus RNA sequencing, single cell RNA sequencing of meningioma cells in co-culture with human cerebral organoids, and RNA sequencing of paired primary and recurrent tumors to develop a single cell transcriptomic atlas of meningioma. These data reveal that clonal genomic instability and subpopulations of cells delineated by misactivation of mesenchymal and immediate early genes define intratumor heterogeneity in meningioma.

No conflict of interest has been declared by the author(s).