PMID- 10086344
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 10
DP  - 1999 Mar 11
TI  - Mutations of c-kit JM domain are found in a minority of human gastrointestinal 
      stromal tumors.
PG  - 1897-902
AB  - The c-kit gene encodes a transmembrane receptor kinase (KIT) which is expressed 
      in the majority of human gastrointestinal stromal tumors (GISTs), a subtype of 
      gastrointestinal mesenchymal neoplasms. A previous study identified mutations in 
      the juxtamembrane (JM) domain of c-kit in five of six GISTs (Science 279: 577, 
      1998). To better define the frequency and spectrum of c-kit gene mutations in 
      mesenchymal neoplasms of the GI tract that had been characterized for KIT protein 
      expression, we examined archived tissue samples for mutations in the JM domain by 
      PCR amplification and DNA sequencing. c-kit JM domain mutations were found in 
      nine of 56 mesenchymal tumors (46 GISTs, eight leiomyomas, two leiomyosarcomas) 
      and occurred exclusively in GISTs (21%). Seven of the nine mutations consisted of 
      intragenic deletions of one to 19 codons. There was one insertion mutation that 
      added 12 codons and one missense mutation (Val560Asp). None of the mutations 
      disrupted the downstream reading frame of the gene. The single missense mutation 
      (Val560Asp) is very similar to the only other missense mutation reported in GISTs 
      (Val599Asp). Of the 46 GISTs, 43 were strongly positive for KIT protein 
      expression and negative for diffuse expression of desmin. Neither KIT expression 
      nor gene mutations were found in gastrointestinal leiomyomas or leiomyosarcomas. 
      We conclude that mutation of the c-kit JM domain does not occur in 
      gastrointestinal mesenchymal neoplasms with well developed-smooth muscle 
      differentiation, and is restricted to GISTs. However, since these mutations are 
      only found in a minority of GISTs, further investigation into the mechanisms of 
      c-kit gene activation in this group of neoplasms is warranted.
FAU - Moskaluk, C A
AU  - Moskaluk CA
AD  - Department of Pathology, University of Virginia, Charlottesville 22908, USA.
FAU - Tian, Q
AU  - Tian Q
FAU - Marshall, C R
AU  - Marshall CR
FAU - Rumpel, C A
AU  - Rumpel CA
FAU - Franquemont, D W
AU  - Franquemont DW
FAU - Frierson, H F Jr
AU  - Frierson HF Jr
LA  - eng
GR  - 5K08CA74431-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Gastrointestinal Neoplasms/*genetics/pathology
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Proto-Oncogene Proteins c-kit/*genetics
MH  - Smooth Muscle Tumor/*genetics/pathology
EDAT- 1999/03/23 03:03
MHDA- 2001/03/28 10:01
CRDT- 1999/03/23 03:03
PHST- 1999/03/23 03:03 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/03/23 03:03 [entrez]
AID - 10.1038/sj.onc.1202496 [doi]
PST - ppublish
SO  - Oncogene. 1999 Mar 11;18(10):1897-902. doi: 10.1038/sj.onc.1202496.