ArticlePloS one2013
Distinct phenotypic differences associated with differential amplification of receptor tyrosine kinase genes at 4q12 in glioblastoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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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.
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.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Genetic Variants Impacting Angiogenesis Signaling Pathways in Glioblastoma Multiforme: A Systematic Review of Mutations and Polymorphisms.Current molecular medicine · 2024Pooled it
- Prognostic value of test(s) for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide.The Cochrane database of systematic reviews · 2021Pooled it
- Favorable Response to Conventional Chemoradiotherapy in Radiation-induced Glioma Harboring Coamplification of PDGFRA, KIT, and KDR: A Case Report and Literature Review.NMC case report journal · 2025Article
- Imaging predictors of 4q12 amplified and RB1 mutated glioblastoma IDH-wildtype.Journal of neuro-oncology · 2024Article
- PDGFRA, KIT, and KDR Gene Amplification in Glioblastoma: Heterogeneity and Clinical Significance.Neuromolecular medicine · 2023Article
- Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry.Frontiers in oncology · 2022Article
- Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma.Journal of neuro-oncology · 2022Article
- Genomic alterations predictive of response to radiosurgery in recurrent IDH-WT glioblastoma.Journal of neuro-oncology · 2021Article
- Article
- Highly Multiplexed Fluorescence in Situ Hybridization for in Situ Genomics.The Journal of molecular diagnostics : JMD · 2019Article
- Clinical and Molecular Characterization of Adult Glioblastomas in Southern Brazil.Journal of neuropathology and experimental neurology · 2019Article
- Genetic and Epigenetic Features of Rapidly Progressing IDH-Mutant Astrocytomas.Journal of neuropathology and experimental neurology · 2018Article
- Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma.Oncology reports · 2017Article
- KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Article
- Prognostic impact ofNeuro-oncology advancesArticle
- The role ofNeuro-oncology advancesArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Gene amplification at chromosome 4q12 is a common alteration in human high grade gliomas including glioblastoma, a CNS tumour with consistently poor prognosis. This locus harbours the known oncogenes encoding the receptor tyrosine kinases PDGFRA, KIT, and VEGFR2. These receptors are potential targets for novel therapeutic intervention in these diseases, with expression noted in tumour cells and/or associated vasculature. Despite this, a detailed assessment of their relative contributions to different high grade glioma histologies and the underlying heterogeneity within glioblastoma has been lacking. We studied 342 primary high grade gliomas for individual gene amplification using specific FISH probes, as well as receptor expression in the tumour and endothelial cells by immunohistochemistry, and correlated our findings with specific tumour cell morphological types and patterns of vasculature. We identified amplicons which encompassed PDGFRA only, PDGFRA/KIT, and PDGFRA/KIT/VEGFR2, with distinct phenotypic correlates. Within glioblastoma specimens, PDGFRA amplification alone was linked to oligodendroglial, small cell and sarcomatous tumour cell morphologies, and rare MGMT promoter methylation. A younger age at diagnosis and better clinical outcome in glioblastoma patients is only seen when PDGFRA and KIT are co-amplified. IDH1 mutation was only found when all three genes are amplified; this is a subgroup which also harbours extensive MGMT promoter methylation. Whilst PDGFRA amplification was tightly linked to tumour expression of the receptor, this was not the case for KIT or VEGFR2. Thus we have identified differential patterns of gene amplification and expression of RTKs at the 4q12 locus to be associated with specific phenotypes which may reflect their distinct underlying mechanisms.
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Registered trials
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.