PMID- 9438854
OWN - NLM
STAT- MEDLINE
DCOM- 19980203
LR  - 20220419
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 279
IP  - 5350
DP  - 1998 Jan 23
TI  - Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.
PG  - 577-80
AB  - 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.
FAU - Hirota, S
AU  - Hirota S
AD  - Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 
      565, Japan.
FAU - Isozaki, K
AU  - Isozaki K
FAU - Moriyama, Y
AU  - Moriyama Y
FAU - Hashimoto, K
AU  - Hashimoto K
FAU - Nishida, T
AU  - Nishida T
FAU - Ishiguro, S
AU  - Ishiguro S
FAU - Kawano, K
AU  - Kawano K
FAU - Hanada, M
AU  - Hanada M
FAU - Kurata, A
AU  - Kurata A
FAU - Takeda, M
AU  - Takeda M
FAU - Muhammad Tunio, G
AU  - Muhammad Tunio G
FAU - Matsuzawa, Y
AU  - Matsuzawa Y
FAU - Kanakura, Y
AU  - Kanakura Y
FAU - Shinomura, Y
AU  - Shinomura Y
FAU - Kitamura, Y
AU  - Kitamura Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Antigens, CD34)
RN  - 0 (DNA, Complementary)
RN  - 0 (Ligands)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Stem Cell Factor)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, CD34/analysis
MH  - Cell Line
MH  - Cell Transformation, Neoplastic
MH  - DNA, Complementary
MH  - Digestive System/cytology
MH  - Esophageal Neoplasms/genetics/metabolism/pathology
MH  - Gastrointestinal Neoplasms/chemistry/*genetics/pathology
MH  - Humans
MH  - Intestinal Neoplasms/chemistry/genetics/pathology
MH  - Ligands
MH  - Mice
MH  - Mice, Nude
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Proto-Oncogene Proteins c-kit/analysis/chemistry/*genetics/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Sequence Deletion
MH  - Stem Cell Factor/pharmacology
MH  - Stomach Neoplasms/genetics/metabolism/pathology
MH  - Transfection
EDAT- 1998/02/07 00:00
MHDA- 1998/02/07 00:01
CRDT- 1998/02/07 00:00
PHST- 1998/02/07 00:00 [pubmed]
PHST- 1998/02/07 00:01 [medline]
PHST- 1998/02/07 00:00 [entrez]
AID - 10.1126/science.279.5350.577 [doi]
PST - ppublish
SO  - Science. 1998 Jan 23;279(5350):577-80. doi: 10.1126/science.279.5350.577.