PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors.
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| Title: | PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors. |
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| Authors: | Heinrich, Michael C., Corless, Christopher L., Duensing, Anette, McCreevey, Laura, Chen, Chang-Jie, Joseph, Nora, Singer, Samuel, Griffith, Diana J., Haley, Andrea, Town, Ajia, Demetri, George D., Fletcher, Christopher D. M., Fletcher, Jonathan A. |
| Source: | Science (pre-March 2025). 1/31/2003, Vol. 299 Issue 5607, p708-710. 3p. 3 Diagrams, 1 Chart, 1 Map. |
| Subjects: | Intestinal tumors, Genetic mutation, Protein-tyrosine kinases |
| Abstract: | Most gastrointestinal stromal tumors (CISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with CISTs respond well to Cleevec, which inhibits KIT kinase activity. Here we show that -35% (14 of 40) of CISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor a (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. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Most gastrointestinal stromal tumors (CISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with CISTs respond well to Cleevec, which inhibits KIT kinase activity. Here we show that -35% (14 of 40) of CISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor a (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. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.1079666 |
