Evidence map›Paper›PMID 40819143›Full record

ArticleNPJ precision oncology2025

Clinical and preclinical insights into a novel MDM2::PDGFRA fusion in recurrent glioblastoma.

Catherine Z Beach, Christopher A Febres-Aldana, Juan Luis Gomez Marti, Saeed Asiry, Tamika Wong, John A Boockvar, Randy S D'Amico, Romel Somwar, Monika A Davare, Morana Vojnic

Abstract read
In one paragraph

Article in NPJ precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

10 authors.

Catherine Z Beach *Department of Pediatrics, Oregon Health Sciences University, Portland, OR, USA.
Christopher A Febres-Aldana *Laboratory of Pathology, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
Juan Luis Gomez MartiDepartment of Pathology, Lenox Hill Hospital, New York, NY, USA.
Saeed AsiryDepartment of Pathology, Lenox Hill Hospital, New York, NY, USA.
Tamika WongDepartment of Neurological Surgery, Lenox Hill Hospital, Northwell, New York, NY, USA.
John A BoockvarDepartment of Neurological Surgery, Lenox Hill Hospital, Northwell, New York, NY, USA.
Randy S D'AmicoDepartment of Neurological Surgery, Lenox Hill Hospital, Northwell, New York, NY, USA.
Romel SomwarDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Monika A DavareDepartment of Pediatrics, Oregon Health Sciences University, Portland, OR, USA. davarem@ohsu.edu.
Morana VojnicRutgers Cancer Institute, New Brunswick, NJ, USA. mv858@cinj.rutgers.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Glioblastoma is an aggressive and treatment-refractory primary brain tumor with limited therapeutic options and high recurrence. The molecular heterogeneity of glioblastoma poses a significant challenge to therapeutic development, as targeted therapies have mostly failed in small-scale clinical trials, underscoring the need for comprehensive next-generation sequencing (NGS) characterization to identify mechanisms of resistance. In this study, we identify and functionally characterize a novel amplified fusion, MDM2 (exon 1)::PDGFRA (exon 8), mediating resistance to cetuximab in an EGFR-amplified glioblastoma. The fusion results in a truncated PDGFRA isoform, in vitro assays demonstrate that MDM2::PDGFRA acts as a constitutively active oncogenic driver with a distinct sensitivity profile to tyrosine kinase inhibitors. Analysis of a glioblastoma cohort indicates PDGFRA structural variants often co-occur with amplification and may serve as biomarkers. These findings highlight the importance of repeat NGS profiling in clinical management and provide a translational framework for identifying and targeting emergent fusion-driven alterations.

Identifiers

PMID40819143
PMCPMC12357959

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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.