Molecular Landscape and Contemporary Prognostic Signatures of Gliomas

Molecularly-driven treatments are expanding options for patients with gliomas, driving a need for molecularly-informed prognostic information. To characterize the genomic landscape and contemporary outcomes of gliomas, we analyzed 4,400 gliomas from multi-institutional datasets and The Cancer Genome Atlas (TCGA): 2,195 glioblastoma, 1,198 IDH1/2 -mutant astrocytoma, 531 oligodendroglioma, 271 other IDH1/2 -wildtype glioma, and 205 pediatric-type glioma. Molecular classification updated 27.4% of gliomas from their original histopathologic diagnosis. Canonical alterations helped categorize glioma subtypes, revealing mutually exclusive alterations within tumorigenic pathways. Across each glioma subtype, non-TCGA patients had longer survival compared to TCGA patients. Several novel prognostic alterations emerged, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2- mutant astrocytoma. Certain prognostic features varied across age, with decreasing prevalence of IDH1/2 -mutation over time while MGMT -methylation remained steady. Our findings provide a framework for further exploration and validation of glioma prognostic indicators in clinically representative cohorts and trials. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of the Dana-Farber/Harvard Cancer Center gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.