Evidence map›Paper›PMID 41553435›Full record

ArticleJournal of neuro-oncology2026

Differences in regional developmental origins of glioblastomas revealed by integrated molecular profiling.

Ryan Gensler, A Karim Ahmed, Melanie Alfonzo Horowitz, Jawad M Khalifeh, Marvin Li, Negar Sadeghipour, Mostafa Abdulrahim, Mike Glantz, Sonikpreet Aulakh, Theodore Nicolaides and 4 more

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Article in Journal of neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Ryan GenslerDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rgensle3@jh.edu.
A Karim AhmedDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Melanie Alfonzo HorowitzDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jawad M KhalifehDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Marvin LiDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Negar SadeghipourCaris Life Sciences, Phoenix, AZ, USA.
Mostafa AbdulrahimDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mike GlantzDepartment of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA.
Sonikpreet AulakhDepartment of Medical Oncology, West Virginia University, Morgantown, WV, USA.
Theodore NicolaidesCaris Life Sciences, Phoenix, AZ, USA.
Calixto-Hope G LucasDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Srinivasan YegnasubramanianSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jordina Rincon-TorroellaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chetan BettegowdaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh-grade IDH-wildtype gliomas are aggressive tumors with marked molecular heterogeneity. This study assessed whether tumor location reflects distinct developmental origins.

methodsWe retrospectively analyzed 5,945 high-grade IDH-wildtype gliomas using de-identified mutational and transcriptomic data. Tumors were grouped as cortical (e.g., frontal, temporal) or deep/dorsal midline (e.g., brainstem, spinal cord). Mutation frequencies, co-mutations, and gene expression profiles were compared.

resultsCortical tumors were enriched for TERT promoter (53.3%), PTEN (34.1%), and EGFR (17.1%) mutations and showed elevated FOXG1, MOXD1, and MEOX2 expression. Deep/dorsal midline tumors had higher rates of H3F3A (22.3%), ATRX (17.5%), FGFR1 (10.1%), and NF1 (27.0%) mutations with increased SOX10, SMOC1, and PPAPDC1A expression. Co-mutation patterns further distinguished subgroups.

conclusionsHigh-grade IDH-wildtype gliomas stratify into cortical NSC-like and deep/dorsal midline OPC-like subtypes, supporting a dual cell-of-origin model and highlighting developmental compartmentalization as a contributor to glioma heterogeneity.

Indexed as

Brain NeoplasmsGlioblastomaMutationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansIsocitrate DehydrogenaseRetrospective StudiesIsocitrate DehydrogenaseAnatomical locationDevelopmental originGlioblastomaIDH-wildtypeMolecular profilingTranscriptomics

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.