PDGFRA activating mutations in gastrointestinal stromal tumors

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

Research output: Contribution to journalArticle

1803 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)708-710
Number of pages3
JournalScience
Volume299
Issue number5607
DOIs
StatePublished - Jan 31 2003

ASJC Scopus subject areas

  • General

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    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. (2003). PDGFRA activating mutations in gastrointestinal stromal tumors. Science, 299(5607), 708-710. https://doi.org/10.1126/science.1079666