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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-2-3
pubmed:abstractText
Activating mutations of KIT and platelet-derived growth factor receptor alpha (PDGFRA) are known to be alternative and mutually exclusive genetic events in the development of gastrointestinal stromal tumors (GISTs). We examined the effect of the mutations of these two genes on the gene expression profile of 22 GISTs using the oligonucleotide microarray. Mutations of KIT and PDGFRA were found in 17 cases and three cases, respectively. The remaining two cases had no detectable mutations in either gene. The mutation status of KIT and PDGFRA was directly related to the expression levels of activated KIT and PDGFRA, and was also related to the different expression levels of activated proteins that play key roles in the downstream of the receptor tyrosine kinase III family. To evaluate the impact of mutation status and the importance of the type of mutation in gene expression and clinical features, microarray-derived data from 22 GISTs were interpreted using a principal component analysis (PCA). Three relevant principal component representing mutation of KIT, PDGFRA and chromosome 14q deletion were identified from the interpretation of the oligonucleotide microarray data with PCA. After supervised analysis, there was at least a two fold difference in expression between GISTs with KIT and PDGFRA mutation in 70 genes. Our findings demonstrate that mutations of KIT and PDGFRA affect differential activation and expression of some genes, and can be used for the molecular classification of GISTs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1066-74
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15690055-Adult, pubmed-meshheading:15690055-Aged, pubmed-meshheading:15690055-Chromosomes, Human, Pair 14, pubmed-meshheading:15690055-DNA Mutational Analysis, pubmed-meshheading:15690055-Female, pubmed-meshheading:15690055-Gastrointestinal Stromal Tumors, pubmed-meshheading:15690055-Gene Expression Profiling, pubmed-meshheading:15690055-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15690055-Humans, pubmed-meshheading:15690055-Male, pubmed-meshheading:15690055-Middle Aged, pubmed-meshheading:15690055-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15690055-Platelet-Derived Growth Factor, pubmed-meshheading:15690055-Principal Component Analysis, pubmed-meshheading:15690055-Proto-Oncogene Proteins c-kit, pubmed-meshheading:15690055-Stomach Neoplasms, pubmed-meshheading:15690055-Transcriptional Activation
pubmed:year
2005
pubmed:articleTitle
Correlation of KIT and platelet-derived growth factor receptor alpha mutations with gene activation and expression profiles in gastrointestinal stromal tumors.
pubmed:affiliation
Department of Pathology, 134 Sichon-dong, Seodaemun-gu, CPO Box 8044, Yonsei University College of Medicine, Seoul 120-752, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't