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Science. 2003 Jan 31;299(5607):708-10. Epub 2003 Jan 9.

PDGFRA activating mutations in gastrointestinal stromal tumors.

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Department of Medicine, Department of Pathology, Oregon Health & Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA.


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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