PDGFRA activating mutations in gastrointestinal stromal tumors.

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.
Authors	Michael C Heinrich, Christopher L Corless, Anette Duensing, Laura McGreevey, Chang-Jie Chen, Nora Joseph, Samuel Singer, Diana J Griffith, Andrea Haley, Ajia Town, George D Demetri, Christopher D M Fletcher, Jonathan A Fletcher
Journal	Science (New York, N.Y.) (Science) Vol. 299 Issue 5607 Pg. 708-10 (Jan 31 2003) ISSN: 1095-9203 [Electronic] United States
PMID	12522257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	DNA-Binding Proteins Proto-Oncogene Proteins STAT1 Transcription Factor STAT1 protein, human STAT3 Transcription Factor STAT3 protein, human Trans-Activators Proto-Oncogene Proteins c-kit Receptor, Platelet-Derived Growth Factor alpha Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Mitogen-Activated Protein Kinases
Topics	Animals CHO Cells Chromosome Aberrations Cricetinae DNA-Binding Proteins (metabolism) Enzyme Activation Exons Gastrointestinal Neoplasms (genetics, metabolism) Humans Karyotyping Mitogen-Activated Protein Kinases (metabolism) Mutation Oncogenes Phosphorylation Protein Serine-Threonine Kinases Proto-Oncogene Proteins (metabolism) Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-kit (genetics, metabolism) Receptor, Platelet-Derived Growth Factor alpha (genetics, metabolism) STAT1 Transcription Factor STAT3 Transcription Factor Signal Transduction Trans-Activators (metabolism)

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