ArticleOncogene2014
PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 81 citations in OpenAlex.
- Targeting Kinase Signaling in Glioblastoma: Structural Optimization, Blood-Brain Barrier Dynamics and Combinatorial Translational Strategies.International journal of molecular sciences · 2026Review
- DriverOmicsNet: an integrated graph convolutional network for multi-omics exploration of cancer driver genes.Briefings in bioinformatics · 2025Article
- Calcifying pseudoneoplasm of the neuraxis progressing to G5/PDGFRA subgroup glioblastoma in a United States Army veteran with a history of head trauma and germline POT1 and EPHB2 mutations: illustrative case.Journal of neurosurgery. Case lessons · 2025Article
- Genetic profiling of osteosarcoma in an adolescent using a next‑generation sequencing panel and Sanger sequencing: A case report and review of the literature.Biomedical reports · 2025Article
- Uterine organoids reveal insights into epithelial specification and plasticity in development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genomic, epigenomic and transcriptomic landscape of glioblastoma.Metabolic brain disease · 2024Review
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- PDGFRA K385 mutants in myxoid glioneuronal tumors promote receptor dimerization and oncogenic signaling.Scientific reports · 2024Article
- On a mechanistic impact of transmembrane tetramerization in the pathological activation of RTKs.Computational and structural biotechnology journal · 2023Article
- NetMix2: A Principled Network Propagation Algorithm for Identifying Altered Subnetworks.Journal of computational biology : a journal of computational molecular cell biology · 2022Article
- High frequency of PDGFRA and MUC family gene mutations in diffuse hemispheric glioma, H3 G34-mutant: a glimmer of hope?Journal of translational medicine · 2022Article
- Review
- MiR-15a-5p Confers Chemoresistance in Acute Myeloid Leukemia by Inhibiting Autophagy Induced by Daunorubicin.International journal of molecular sciences · 2021Article
- PDGF receptor mutations in human diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer.Frontiers in pharmacology · 2021Review
- Association of Extracellular Signal-Regulated Kinase Genes With Myopia: A Longitudinal Study of Chinese Children.Frontiers in genetics · 2021Article
- Genetic analyses in mouse fibroblast and melanoma cells demonstrate novel roles for PDGF-AB ligand and PDGF receptor alpha.Scientific reports · 2020Article
- SMARCB1 Gene Mutation Predisposes to Earlier Development of Glioblastoma: A Case Report of Familial GBM.Journal of neuropathology and experimental neurology · 2020Article
- Membrane receptor activation mechanisms and transmembrane peptide tools to elucidate them.The Journal of biological chemistry · 2020Review
- Expression of Alpha-type Platelet-derived Growth Factor Receptor-influenced Genes Predicts Clinical Outcome in Glioma.Translational oncology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating mutations in the platelet-derived growth factor (PDGF) receptor alpha (PDGFRA) have been described in patients with gastrointestinal stromal tumors or myeloid malignancies associated with hypereosinophilia. These patients respond well to imatinib mesylate, raising the question as to whether patients with a PDGF receptor mutation in other tumor types should receive a tyrosine kinase inhibitor treatment. We characterized 10 novel somatic point mutations in PDGFRA that have been reported in isolated cases of glioblastoma, melanoma, acute myeloid leukemia, peripheral nerve sheath tumors and neuroendocrine carcinoma. The PDGFRA transmembrane domain mutation V536E stimulated Ba/F3 cell growth and signaling via ERK and STAT5 in the absence of ligand. This mutant, identified in glioblastoma, was strongly inhibited by imatinib. Modeling suggested that the mutation modulates the packing of the transmembrane domain helices in the receptor dimer. By contrast, two mutations in highly conserved residues affected the receptor traffic to the cell surface or kinase activity, thereby preventing the response to PDGF. The other mutations had no significant impact on the receptor activity. This functional analysis matched the predictions of SIFT and PolyPhen for only five mutations and these algorithms do not discriminate gain from loss of function. Finally, an E996K variant that had been identified in a melanoma cell line was not expressed in these cells. Altogether, several newly identified PDGFRA mutations do not activate the receptor and may therefore represent passenger mutations. Our results also underline the importance of characterizing novel kinase alterations in cancer patients.
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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 Socratic graph.