title: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.
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.
authors.affiliation: Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hirota
authors.forename: K
authors.initials: K
authors.lastname: Isozaki
authors.forename: Y
authors.initials: Y
authors.lastname: Moriyama
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Nishida
authors.forename: S
authors.initials: S
authors.lastname: Ishiguro
authors.forename: K
authors.initials: K
authors.lastname: Kawano
authors.forename: M
authors.initials: M
authors.lastname: Hanada
authors.forename: A
authors.initials: A
authors.lastname: Kurata
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: G
authors.initials: G
authors.lastname: Muhammad Tunio
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kanakura
authors.forename: Y
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D018076:DNA, Complementary; D004064:Digestive System / Q000166:cytology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007414:Intestinal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D017384:Sequence Deletion; D019089:Stem Cell Factor / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: D018952:Antigens, CD34; D018076:DNA, Complementary; D008024:Ligands; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019000:Phosphotyrosine; D019009:Proto-Oncogene Proteins c-kit