PDGFRA activating mutations in gastrointestinal stromal tumors Journal Article


Authors: Heinrich, M. C.; Corless, C. L.; Duensing, A.; McGreevey, L.; Chen, C. J.; Joseph, N.; Singer, S.; Griffith, D. J.; Haley, A.; Town, A.; Demetri, G. D.; Fletcher, C. D. M.; Fletcher, J. A.
Article Title: 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 ∼35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor α (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.
Keywords: signal transduction; oncoprotein; gene mutation; mutation; dna-binding proteins; exons; proto-oncogene proteins; animals; gastrointestinal stromal tumor; imatinib; platelet derived growth factor alpha receptor; proto-oncogene proteins c-kit; receptor, platelet-derived growth factor alpha; enzyme inhibition; gene expression; biology; cytogenetics; enzyme activation; protein tyrosine kinase; phosphorylation; oncogenes; gastrointestinal neoplasms; gene activation; tumors; protein-serine-threonine kinases; proto-oncogene proteins c-akt; stat3 transcription factor; trans-activators; chromosome aberrations; tumor growth; mitogen-activated protein kinases; karyotyping; diseases; enzymes; cho cells; cricetinae; gastroenterology; stat1 transcription factor; humans; priority journal; article; gastrointestinal stromal tumors (gist)
Journal Title: Science
Volume: 299
Issue: 5607
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2003-01-31
Start Page: 708
End Page: 710
Language: English
DOI: 10.1126/science.1079666
PUBMED: 12522257
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Samuel Singer
    233 Singer