Evidence map›Paper›PMID 40514380›Full record

ArticleNature communications2025

Resolving spatial subclonal genomic heterogeneity of loss of heterozygosity and extrachromosomal DNA in gliomas.

Michelle G Webb, Frances Chow, Carmel G McCullough, Bohan Zhang, John J Y Lee, Rania Bassiouni, Norman E Garrett, Kyle Hurth, John D Carpten, Gabriel Zada and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Michelle G WebbDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-7613-5759
Frances ChowDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-5402-2473
Carmel G McCulloughDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2092-7180
Bohan ZhangDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0007-1439-7730
John J Y LeeDepartment of Integrative Translational Sciences, City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-7967-3384
Rania BassiouniDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-4754-9311
Norman E GarrettDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0003-1287-2498
Kyle HurthDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
John D CarptenDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Gabriel ZadaDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Gabriel.Zada@med.usc.edu.
David W CraigDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. dacraig@coh.org.ORCID http://orcid.org/0000-0003-2040-1955

Funding

Mentored Career DevelopmentKL2TR001854 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Elizabeth Rhea Erwin Burner, Amy Elizabeth West · 2016 to 2026
$9.0M
NCATS NIH HHS KL2 TR001854
6 · The paper itself

Abstract

Mapping the spatial organization of DNA-level somatic copy number changes in tumors can provide insight to understanding higher-level molecular and cellular processes that drive pathogenesis. We describe an integrated framework of spatial transcriptomics, tumor/normal DNA sequencing, and bulk RNA sequencing to identify shared and distinct characteristics of an initial cohort of eleven gliomas of varied pathology and a replication cohort of six high-grade glioblastomas. We identify focally amplified extrachromosomal DNA (ecDNA) in four of the eleven initial gliomas, with subclonal tumor heterogeneity in two EGFR-amplified grade IV glioblastomas. In a TP53-mutated glioblastoma, we detect a subclone with EGFR amplification on ecDNA coupled to chromosome 17 loss of heterozygosity. To validate subclonal somatic aneuploidy and copy number alterations associated with ecDNA double minutes, we examine the replication cohort, identifying MDM2/MDM4 ecDNA subclones in two glioblastomas. The spatial heterogeneity of EGFR and p53 inactivation underscores the role of ecDNA in enabling rapid oncogene amplification and enhancing tumor adaptability under selective pressure.

Indexed as

Brain NeoplasmsGliomaLoss of HeterozygosityDNA Copy Number VariationsErbB ReceptorsFemaleGene AmplificationGenetic HeterogeneityGlioblastomaHumansMaleMiddle AgedMutationProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53EGFR protein, humanErbB ReceptorsMDM2 protein, humanProto-Oncogene Proteins c-mdm2TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID40514380
PMCPMC12166086

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Registered trials

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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.