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辐射诱发胶质母细胞瘤的独特分子特征。

Unique molecular characteristics of radiation-induced glioblastoma.

作者信息

Donson Andrew M, Erwin Nicole S, Kleinschmidt-DeMasters B K, Madden Jennifer R, Addo-Yobo Steven O, Foreman Nicholas K

机构信息

Department of Pediatrics, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.

出版信息

J Neuropathol Exp Neurol. 2007 Aug;66(8):740-9. doi: 10.1097/nen.0b013e3181257190.

Abstract

Radiation-induced glioblastomas (RIGs) represent a significant proportion of glioblastomas (GBMs) seen in children and young adults and manifest poor prognosis. Little is known about their underlying biology, although limited studies have suggested no unique histologic or cytogenetic characteristics to distinguish them from de novo GBMs. In this study, we confirmed that a series of 5 RIGs showed no unique histologic or cytogenetic features compared with de novo pediatric GBMs, prompting us to further investigate RIGs using gene expression microarray profiling and Western blot analysis. Despite the inability of histologic and molecular genetic studies to identify distinguishing features between RIGs and pediatric GBMs, gene microarrays suggested significant differences between these 2 tumor types, at least those occurring in pediatric patients. Pediatric RIGs show greater homogeneity of gene expression than do de novo pediatric GBMs. Greater overlap was detected in gene expression patterns between RIGs and pilocytic astrocytomas than between RIGs and GBMs, medulloblastomas, ependymomas, atypical teratoid rhabdoid tumors, or rhabdomyosarcomas, suggesting a common precursor cell for RIG and pilocytic astrocytoma. Western blot analyses confirmed that ErbB3, Sox10, and platelet-derived growth factor receptor-alpha proteins were consistently expressed in RIGs but rarely in pediatric GBMs.

摘要

辐射诱发的胶质母细胞瘤(RIG)在儿童和年轻成人中占胶质母细胞瘤(GBM)的很大比例,且预后较差。尽管有限的研究表明,与原发性GBM相比,RIG没有独特的组织学或细胞遗传学特征,但对其潜在生物学特性知之甚少。在本研究中,我们证实,与原发性儿童GBM相比,一系列5例RIG没有独特的组织学或细胞遗传学特征,这促使我们使用基因表达微阵列分析和蛋白质印迹分析进一步研究RIG。尽管组织学和分子遗传学研究无法识别RIG与儿童GBM之间的区别特征,但基因微阵列显示这两种肿瘤类型之间存在显著差异,至少在儿童患者中如此。儿童RIG比原发性儿童GBM表现出更高的基因表达同质性。与RIG和GBM、髓母细胞瘤、室管膜瘤、非典型畸胎样横纹肌样肿瘤或横纹肌肉瘤相比,RIG与毛细胞型星形细胞瘤之间的基因表达模式有更大的重叠,这表明RIG和毛细胞型星形细胞瘤有共同的前体细胞。蛋白质印迹分析证实,ErbB3、Sox10和血小板衍生生长因子受体α蛋白在RIG中持续表达,但在儿童GBM中很少表达。

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