ArticleOncogene2003
A human brain tumor-derived PDGFR-alpha deletion mutant is transforming.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 109 citations in OpenAlex.
- Targeting Kinase Signaling in Glioblastoma: Structural Optimization, Blood-Brain Barrier Dynamics and Combinatorial Translational Strategies.International journal of molecular sciences · 2026Review
- Gene Mutations and Related Molecular Events in Distant Metastasis of Cervical Cancer: A Review.International journal of medical sciences · 2026Review
- Mutant IDH impairs chromatin binding by PDGFB to promote chromosome instability.bioRxiv : the preprint server for biology · 2025Article
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
- Oncogenic long noncoding RNA LINC02283 enhances PDGF receptor A-mediated signaling and drives glioblastoma tumorigenesis.Neuro-oncology · 2023Article
- Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors.Cancers · 2022Review
- CircCDK14 Promotes Tumor Progression and Resists Ferroptosis in Glioma by Regulating PDGFRA.International journal of biological sciences · 2022Article
- Opposed Interplay between IDH1 Mutations and the WNT/β-Catenin Pathway: Added Information for Glioma Classification.Biomedicines · 2021Review
- Dysregulated PDGFR alpha expression and novel somatic mutations in colorectal cancer: association to RAS wild type status and tumor size.Journal of translational medicine · 2020Article
- The Unwanted Cell Migration in the Brain: Glioma Metastasis.Neurochemical research · 2017Review
- Article
- Influences of Anlotinib on Cytochrome P450 Enzymes in Rats Using a Cocktail Method.BioMed research international · 2017Article
- The Role of PDGFs and PDGFRs in Colorectal Cancer.Mediators of inflammation · 2017Review
- Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas.Molecular systems biology · 2016Article
- Platelet-derived growth factor receptor/platelet-derived growth factor (PDGFR/PDGF) system is a prognostic and treatment response biomarker with multifarious therapeutic targets in cancers.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma.CNS oncology · 2016Review
- Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer.PLoS genetics · 2015Article
- A point mutation in the extracellular domain of KIT promotes tumorigenesis of mast cells via ligand-independent auto-dimerization.Scientific reports · 2015Article
- Constitutive activation of oncogenic PDGFRα-mutant proteins occurring in GIST patients induces receptor mislocalisation and alters PDGFRα signalling characteristics.Cell communication and signaling : CCS · 2015Article
- Molecularly targeted therapies for recurrent glioblastoma: current and future targets.Neurosurgical focus · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant receptor tyrosine kinase signaling plays an important role in the molecular pathogenesis of brain tumors. We have been studying a previously identified human glioblastoma-derived PDGFR-alpha mutant that has an in-frame deletion in the extracellular domain, causing loss of exons 8 and 9 (PDGFR-alpha(delta8,9)). In the primary tumor, this deletion mutant receptor was shown to be amplified and overexpressed. The purpose of this study was to determine the expression, activity, localization, and transformation properties of this deletion mutant. In the absence of serum, or PDGF-AA, PDGFR-alpha(delta8,9) was phosphorylated on tyrosine residues, indicating ligand-independent autoactivation. Localization by staining and cell surface biotinylation studies revealed expression of the deletion mutant predominantly in the cytoplasm, with very little present on the cell surface. To determine if PDGFR-alpha(delta8,9) was oncogenic, we transfected wild-type and mutant receptors into Rat1 cells and performed analyses of cell growth, in vitro transformation, and subcutaneous growth in the nude mouse. PDGFR-alpha(delta8,9)-expressing cells displayed enhanced cell growth and survival in low serum, and formed foci in monolayer cultures. PDGFR-alpha(delta8,9)-expressing Rat1 cells were also tumorigenic when injected subcutaneously into nude mice. Expression of PDGFR-alpha(delta8,9) was also associated with increased c-Jun phosphorylation in the absence of PDGF ligand, demonstrating also that the mutant receptor is associated with altered intracellular signaling. These data demonstrate that PDGFR-alpha(delta8,9) is transforming, and it is the first demonstration of a naturally occurring tumor-derived mutant PDGFR-alpha with oncogenic properties.
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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.