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- Title
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.
- Authors
Hirota, S; Isozaki, K; Moriyama, Y; Hashimoto, K; Nishida, T; Ishiguro, S; Kawano, K; Hanada, M; Kurata, A; Takeda, M; Muhammad Tunio, G; Matsuzawa, Y; Kanakura, Y; Shinomura, Y; Kitamura, Y
- Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.
- Publication
Science (New York, N.Y.), 1998, Vol 279, Issue 5350, p577
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.279.5350.577