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

doi:10.1126/science.1079666

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

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2092 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 language	English (US)
Pages (from-to)	708-710
Number of pages	3
Journal	Science
Volume	299
Issue number	5607
DOIs	https://doi.org/10.1126/science.1079666
State	Published - Jan 31 2003

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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.",

author = "Heinrich, {Michael C.} and Corless, {Christopher L.} and Anette Duensing and Laura McGreevey and Chen, {Chang Jie} and Nora Joseph and Samuel Singer and Griffith, {Diana J.} and Andrea Haley and Ajia Town and Demetri, {George D.} and Fletcher, {Christopher D.M.} and Fletcher, {Jonathan A.}",

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T1 - PDGFRA activating mutations in gastrointestinal stromal tumors

AU - Heinrich, Michael C.

AU - Corless, Christopher L.

AU - Duensing, Anette

AU - McGreevey, Laura

AU - Chen, Chang Jie

AU - Joseph, Nora

AU - Singer, Samuel

AU - Griffith, Diana J.

AU - Haley, Andrea

AU - Town, Ajia

AU - Demetri, George D.

AU - Fletcher, Christopher D.M.

AU - Fletcher, Jonathan A.

PY - 2003/1/31

Y1 - 2003/1/31

N2 - 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.

AB - 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.

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PDGFRA activating mutations in gastrointestinal stromal tumors

Abstract

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