PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors

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Science  31 Jan 2003:
Vol. 299, Issue 5607, pp. 708-710
DOI: 10.1126/science.1079666

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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 KITmutations 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.

  • * To whom correspondence should be addressed. E-mail: heinrich{at}, jfletcher{at}

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