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      PDGFRA activating mutations in gastrointestinal stromal tumors.

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          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.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Jan 31 2003
          : 299
          : 5607
          Affiliations
          [1 ] Department of Medicine, Department of Pathology, Oregon Health & Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA. heinrich@ohsu.edu
          Article
          1079666
          10.1126/science.1079666
          12522257
          27d657dd-7676-4490-a67b-a522b2edabfb
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