PMID- 15869870
OWN - NLM
STAT- MEDLINE
DCOM- 20050729
LR  - 20220317
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1741
IP  - 1-2
DP  - 2005 Jun 30
TI  - KIT overexpression and amplification in gastrointestinal stromal tumors (GISTs).
PG  - 165-72
AB  - The tyrosine kinase receptor KIT plays a major role in gastrointestinal stromal 
      tumors (GISTs) oncogenesis. Indeed, 95% of GISTs express KIT protein, and about 
      70% exhibit activating mutations of the KIT gene. However, little is known about 
      KIT overexpression mechanisms in these tumors, and the correlation with KIT 
      mutations. GISTs with mutations within exon 11 (n=12) or 9 (n=1) of KIT were 
      compared with GISTs without KIT mutations in exons 9, 11, 13, and 17 (n=10), two 
      of them had PDGFRA mutations. KIT amplification was studied by real-time PCR of 
      KIT and beta-ACTIN genes, and by fluorescence in situ hybridization (FISH) using 
      KIT and chromosome 4 centromere specific probes. KIT transcripts and protein 
      expression were quantified by reverse transcription real-time PCR and Western 
      blot respectively. Genomic analysis revealed a single mutated GIST with KIT 
      amplification. KIT protein and RNA levels were highly variable in GISTs but 
      closely correlated (r=0.82, P<1.10(-5)), and were higher in GISTs with KIT 
      mutations (P=0.07 and P=0.03 respectively). In conclusion, contrasting with the 
      regulation of other tyrosine kinase receptors, KIT overexpression in GISTs is 
      rarely related to a gene amplification, which suggests a deregulation of KIT gene 
      transcription.
FAU - Tabone, Severine
AU  - Tabone S
AD  - Biochemistry and Molecular Biology Department, Paul Brousse Hospital, AP-HP, 
      INSERM U602, Paris Sud University, Villejuif 94804, France.
FAU - Theou, Nathalie
AU  - Theou N
FAU - Wozniak, Agnieszka
AU  - Wozniak A
FAU - Saffroy, Raphael
AU  - Saffroy R
FAU - Deville, Laure
AU  - Deville L
FAU - Julie, Catherine
AU  - Julie C
FAU - Callard, Patrice
AU  - Callard P
FAU - Lavergne-Slove, Anne
AU  - Lavergne-Slove A
FAU - Debiec-Rychter, Maria
AU  - Debiec-Rychter M
FAU - Lemoine, Antoinette
AU  - Lemoine A
FAU - Emile, Jean-Francois
AU  - Emile JF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050413
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Chromosomes, Human, Pair 4
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/genetics
MH  - Exons
MH  - Female
MH  - Gastrointestinal Stromal Tumors/genetics/*metabolism/pathology
MH  - *Gene Amplification
MH  - *Gene Expression
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Proto-Oncogene Proteins c-kit/genetics/*metabolism
MH  - Receptor, Platelet-Derived Growth Factor alpha/genetics
EDAT- 2005/05/05 09:00
MHDA- 2005/07/30 09:00
CRDT- 2005/05/05 09:00
PHST- 2004/10/11 00:00 [received]
PHST- 2005/03/10 00:00 [revised]
PHST- 2005/03/22 00:00 [accepted]
PHST- 2005/05/05 09:00 [pubmed]
PHST- 2005/07/30 09:00 [medline]
PHST- 2005/05/05 09:00 [entrez]
AID - S0925-4439(05)00030-X [pii]
AID - 10.1016/j.bbadis.2005.03.011 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2005 Jun 30;1741(1-2):165-72. doi: 
      10.1016/j.bbadis.2005.03.011. Epub 2005 Apr 13.