Insulin-like growth factor 1 receptor expression in wild-type GISTs: A potential novel therapeutic target

Insulin-like growth factor 1 receptor expression in wild-type GISTs: A potential novel therapeutic target
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DOI:
10.1002/ijc.24595
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发表时间:
2009-12-15
影响因子:
6.4
通讯作者:
Biasco, Guido
Biasco, Guido
中科院分区:
医学1区
文献类型:
--
作者:
Pantaleo, Maria A.;Astolfi, Annalisa;Biasco, Guido

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已发现胰岛素样生长因子 (IGF) 系统的异常与多种癌症类型有关。 IGF1R 的潜在作用已被假设在一小部分 GIST 中,但迄今为止其畸变的影响尚未确定。该研究的目的是检查胃 GIST 患者的 IGF1R 状态的 KIT 和 PDGFRA 基因型。从 8 个原发性肿瘤 [2 个野生型 (WT) 和 6 个突变病例] 采集新鲜切除标本。使用 Affymetrix GeneChip HG-U133Plus 2.0 阵列对 IGF1R 进行基因表达分析,使用 SNP 阵列分析 Affymetrix Genome Wide Human SNP 6.0 阵列进行基因组拷贝数研究,并使用蛋白质印迹 (WB) 和免疫组织化学 (IHC) 进行蛋白质水平研究。对我们患者的基因表达谱进行无监督分析,并与胃 GIST 的数据集相结合,确定 8 名患者中有 2 名具有不同的 IGF1R 表达。该数据得到了 WB 和 IHC 的确认。特别是,IGF1R 在 2 名年轻患者中表达上调(
Aberrations of the Insulin-like Growth Factor (IGF) system have been found in association with a variety of cancer types. The potential role of IGF1R has been postulated in a small subset of GISTs, but until now the implications of its aberrations have not been defined. The aim of the study was to examine the IGF1R status in patients with gastric GIST in regard to KIT and PDGFRA genotype. Fresh resection specimens were collected from 8 primary tumours [2 wild-type (WT) and 6 mutant cases]. IGF1R was studied as gene expression profiling with Affymetrix GeneChip HG-U133Plus 2.0 arrays and as genomic copy number with SNP array analysis Affymetrix Genome Wide Human SNP 6.0 arrays, and at protein level with western blotting (WB) and immunohistochemistry (IHC). The unsupervised analysis of gene expression profiling of our patients merged with a data set from gastric GISTs identified 2 patients out of 8 with different expression of IGF1R. The data were confirmed by WB and IHC. In particular, IGF1R was upregulated in 2 young patients (