Hypermitotic meningiomas harbor DNA methylation subgroups with distinct biological and clinical features

alexandrossfakianakis shared this article with you from Inoreader Hypermitotic meningiomas harbor DNA methylation subgroups with distinct biological and clinical features via Neuro-Oncology Advance Access Abstract Background Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology. Methods 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n=200) or validation (n=365) institutions were re-analyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation groups. RNA sequencing from the discovery (n=200) or validation (n=302) cohort were analyzed in the context of DNA methylation groups to identify subgroups. Biological featur es and clinical outcomes were analyzed across meningioma grouping schemes. Results RNA sequencing revealed differential enrichment of FOXM1 target genes across 2 subgroups of Hypermitotic meningiomas. Differential expression and ontology analyses showed the subgroup of Hypermitotic meningiomas without FOXM1 target gene enrichment was distinguished by gene expression programs driving macromolecular metabolism. Analysis of genetic, epigenetic, gene expression, or cellular features revealed Hypermitotic meningioma subgroups were concordant with Proliferative or Hypermetabolic meningiomas, which were previously reported alongside Merlin-intact and Immune-enriched tumors using an integrated molecular model. The addition of DNA methylation subgroups to clinical models refined prediction of postoperative outcomes compared to the addition of DNA methylation groups. Conclusions Meningiomas can be separated into 3 DNA methylation groups and Hypermitotic meningiomas can be su bdivided into Proliferative and Hypermetabolic subgroups, each with distinct biological and clinical features. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.