Evidence map›Paper›PMID 39560080›Full record

ArticleNeuro-oncology2025

Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses.

Calixto-Hope G Lucas, Nadeem N Al-Adli, Jacob S Young, Rohit Gupta, Ramin A Morshed, Jasper Wu, Ajay Ravindranathan, Anny Shai, Nancy Ann Oberheim Bush, Jennie W Taylor and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. MedComm · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. A Genomically Tailored Multiagent Precision Medicine Clinical Trial for Adults with Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Promoter Methylation-Expression Coupling of Gliogenesis Genes inInternational journal of molecular sciences · 2026
    Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
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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

29 authors.

Calixto-Hope G LucasUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0002-8347-9592
Nadeem N Al-AdliUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Jacob S YoungUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Rohit GuptaUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Ramin A MorshedUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Jasper WuUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Ajay RavindranathanUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Anny ShaiUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Nancy Ann Oberheim BushUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0001-8302-5008
Jennie W TaylorUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
John de GrootUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0003-1454-6461
Javier E Villanueva-MeyerUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Melike PekmezciUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Arie PerryUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Andrew W BollenUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Philip V TheodosopoulosUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Manish K AghiUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Edward F ChangUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Shawn L Hervey-JumperUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0003-4699-260X
David R RaleighUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0001-9299-8864
Annette M MolinaroUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Joseph F CostelloUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Aaron A DiazUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0001-9059-9501
Jennifer L ClarkeUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0002-8054-7342
Nicholas A ButowskiUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Joanna J PhillipsUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
Susan M ChangUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0003-3521-364X
Mitchel S BergerUCSF Brain Tumor Center, University of California, San Francisco, California, USA.
David A SolomonUCSF Brain Tumor Center, University of California, San Francisco, California, USA.ORCID 0000-0003-4571-7999

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
Mechanisms of Hedgehog signaling in glioblastomaR01CA251221 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RALEIGH, DAVID R · 2021 to 2025
$2.6M
Retroviral RLI immunomodulatory gene therapy for glioblastomaR01NS123808 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Manish Aghi · 2022 to 2026
$2.1M
An informatics framework for single-cell multi-omics from clinical specimensR01LM013897 · NLM · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aaron Antonio Diaz · 2022 to 2026
$1.8M
Gilbert Family FoundationNCI NIH HHS P50 CA097257NCI NIH HHS R01 CA251221NCI NIH HHS T32 CA151022NIH HHS T32 CA151022NINDS NIH HHS R01 NS123808NLM NIH HHS R01 LM013897Panattoni Family FoundationSandler Foundation
6 · The paper itself

Abstract

backgroundDespite recent advances in the biology of IDH-wildtype glioblastoma, it remains a devastating disease with median survival of less than 2 years. However, the molecular underpinnings of the heterogeneous response to the current standard-of-care treatment regimen consisting of maximal safe resection, adjuvant radiation, and chemotherapy with temozolomide remain unknown.

methodsComprehensive histopathologic, genomic, and epigenomic evaluation of paired initial and recurrent glioblastoma specimens from 106 patients was performed to investigate the molecular evolution and cellular phenotypes underlying differential treatment responses.

resultsWhile TERT promoter mutation and CDKN2A homozygous deletion were early events during gliomagenesis shared by initial and recurrent tumors, most other recurrent genetic alterations (eg, EGFR, PTEN, and NF1) were commonly private to initial or recurrent tumors indicating acquisition later during clonal evolution. Furthermore, glioblastomas exhibited heterogeneous epigenomic evolution with subsets becoming more globally hypermethylated, hypomethylated, or remaining stable. Glioblastoma that underwent sarcomatous transformation had shorter interval to recurrence and were significantly enriched in NF1, TP53, and RB1 alterations and the mesenchymal epigenetic class. Patients who developed somatic hypermutation following temozolomide treatment had significantly longer interval to disease recurrence and prolonged overall survival, and increased methylation at 4 specific CpG sites in the promoter region of MGMT was significantly associated with this development of hypermutation. Finally, an epigenomic evolution signature incorporating change in DNA methylation levels across 347 critical CpG sites was developed that significantly correlated with clinical outcomes.

conclusionsGlioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.

Indexed as

Biomarkers, TumorBrain NeoplasmsGlioblastomaIsocitrate DehydrogenaseMutationNeoplasm Recurrence, LocalAdultAgedDNA MethylationEpigenesis, GeneticFemaleFollow-Up StudiesHumansMaleMiddle AgedPhenotypeBiomarkers, TumorIDH1 protein, humanIsocitrate DehydrogenaseDNA methylationglioblastomagliosarcomamolecular neuropathologytemozolomide-induced hypermutation

Identifiers

PMID39560080
PMCPMC11726253

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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.