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Correlation of KIT and platelet-derived growth factor receptor α mutations with gene activation and expression profiles in gastrointestinal stromal tumors

 Hyun Ju Kang  ;  Suk Woo Nam  ;  Hyunki Kim  ;  Hwanseok Rhee  ;  Nam-Gyun Kim  ;  Haeryoung Kim  ;  Woo Jin Hyung  ;  Sung Hoon Noh  ;  Joo-Hang Kim  ;  Chae-Ok Yun  ;  Edison T Liu  ;  Hoguen Kim 
 ONCOGENE, Vol.24(6) : 1066-1074, 2005 
Journal Title
Issue Date
Adult ; Aged ; Chromosomes, Human, Pair 14/genetics ; DNA Mutational Analysis ; Female ; Gastrointestinal Stromal Tumors/genetics* ; Gastrointestinal Stromal Tumors/pathology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic* ; Humans ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Platelet-Derived Growth Factor/genetics* ; Principal Component Analysis ; Proto-Oncogene Proteins c-kit/genetics* ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/pathology ; Transcriptional Activation
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.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyun Ju(강현주)
Kim, Joo Hang(김주항)
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hae Ryoung(김혜령)
Kim, Hogeun(김호근)
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Yun, Chae Ok(윤채옥)
Rhee, Hwan Seok(이환석)
Hyung, Woo Jin(형우진) ORCID logo https://orcid.org/0000-0002-8593-9214
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