Topic
PDGFRA
About: PDGFRA is a research topic. Over the lifetime, 1759 publications have been published within this topic receiving 83583 citations. The topic is also known as: CD140A & PDGFR-2.
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Harvard University1, University of North Carolina at Chapel Hill2, University of California, Berkeley3, Washington University in St. Louis4, Lawrence Berkeley National Laboratory5, University of California, San Francisco6, Mayo Clinic7, Memorial Sloan Kettering Cancer Center8, SRA International9, Walter and Eliza Hall Institute of Medical Research10
TL;DR: A robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes is described and multidimensional genomic data is integrated to establish patterns of somatic mutations and DNA copy number.
5,764 citations
Harvard University1, University of North Carolina at Chapel Hill2, University of California, Berkeley3, Washington University in St. Louis4, Lawrence Berkeley National Laboratory5, University of California, San Francisco6, Mayo Clinic7, Memorial Sloan Kettering Cancer Center8, SRA International9, Walter and Eliza Hall Institute of Medical Research10
TL;DR: The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM) and proposed a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes as discussed by the authors.
Abstract: The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.
4,464 citations
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Memorial Sloan Kettering Cancer Center1, Broad Institute2, Heidelberg University3, University of São Paulo4, University of California, Santa Cruz5, Harvard University6, Institute for Systems Biology7, University of Texas MD Anderson Cancer Center8, Case Western Reserve University9, Henry Ford Health System10, Duke University11, Emory University12, University of California, San Francisco13, Cedars-Sinai Medical Center14, St. Joseph's Hospital and Medical Center15, University of Florida16, Thomas Jefferson University17, University of Toronto18, Christiana Care Health System19, Mayo Clinic20, Penrose Hospital21, University of Southern California22, University of North Carolina at Chapel Hill23, Baylor College of Medicine24, University of British Columbia25, Oregon Health & Science University26, Washington University in St. Louis27
TL;DR: Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM.
3,593 citations
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TL;DR: Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression, suggesting KIT and PDGFra mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.
Abstract: Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.
2,249 citations
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TL;DR: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib.
Abstract: Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. Patients and Methods: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. Results: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation ...
2,180 citations