Correlation of KIT and platelet-derived growth factor receptor α mutations with gene activation and expression profiles in gastrointestinal stromal tumors
Correlation of KIT and platelet-derived growth factor receptor α mutations with gene activation and expression profiles in gastrointestinal stromal tumors
复制标题
DOI：
10.1038/sj.onc.1208358
复制
发表时间：
2005-02-03
期刊：
影响因子：
8
通讯作者：
Kim, HG
中科院分区：
文献类型：
--
作者：
Kang, HJ;Nam, SW;Kim, HG
众所周知，KIT 和血小板源性生长因子受体 α (PDGFRA) 的激活突变是胃肠道间质瘤 (GIST) 发展过程中的替代且相互排斥的遗传事件。我们检查了这两个基因的突变对基因表达亲的影响。使用寡核苷酸微阵列分析 22 个 GIST。分别在17例和3例中发现KIT和PDGFRA突变。其余两个病例的任一基因均未检测到突变。 KIT和PDGFRA的突变状态与激活的KIT和PDGFRA的表达水平直接相关，也与受体酪氨酸激酶III家族下游起关键作用的激活蛋白的不同表达水平有关。为了评估突变状态的影响以及突变类型对基因表达和临床特征的重要性，使用主成分分析 (PCA) 解释了来自 22 个 GIST 的微阵列数据。通过 PCA 对寡核苷酸微阵列数据的解释，鉴定出代表 KIT、PDGFRA 突变和染色体 14q 缺失的三个相关主要成分。经过监督分析，KIT 和 PDGFRA 突变的 GIST 之间的 70 个基因的表达存在至少两倍的差异。我们的研究结果表明，KIT 和 PDGFRA 的突变影响某些基因的差异激活和表达，可用于 GIST 的分子分类。
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 pro. le 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.