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

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Abstract

Activating mutations of KIT and platelet-derived growth factor receptor α (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.

Original languageEnglish
Pages (from-to)1066-1074
Number of pages9
JournalOncogene
Volume24
Issue number6
DOIs
Publication statusPublished - 2005 Feb 3

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Kang, H. J., Nam, S. W., Kim, H., Rhee, H., Kim, N. G., Kim, H., Hyung, W. J., Noh, S. H., Kim, J. H., Yun, C. O., Liu, E. T., & Kim, H. (2005). Correlation of KIT and platelet-derived growth factor receptor α mutations with gene activation and expression profiles in gastrointestinal stromal tumors. Oncogene, 24(6), 1066-1074. https://doi.org/10.1038/sj.onc.1208358