Characterization of the amplicon on chromosomal segment 4q12 in glioblastoma multiforme
Characterization of the amplicon on chromosomal segment 4q12 in glioblastoma multiforme
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DOI：
10.1215/15228517-2007-009
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发表时间：
2007-07-01
期刊：
影响因子：
15.9
通讯作者：
von Deimling, Andreas
中科院分区：
文献类型：
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作者：
Holtkamp, Nikola;Ziegenhagen, Nicolas;von Deimling, Andreas
胶质母细胞瘤（GBMs）的一个亚群在染色体4q12片段上携带基因扩增。为了详细表征该扩增子，我们分析了一组100个样本，包括65个GBMs， 10个WHO III级星形细胞瘤，12个少突胶质细胞瘤和13个胶质瘤细胞培养物。我们使用多重连接依赖探针扩增来测定PDGFRA、KIT和KDR及其侧基因USP46、RASL11B、LNX1、CHIC2、SEC3L1和IGFBP7的基因剂量。扩增子的大小和拷贝数变化很大，扩增区域可达5mb。在15%的GBM细胞培养物和23%的GBM细胞培养物中观察到4q12扩增，但在22个其他胶质瘤中未观察到。我们分析了该扩增子内一些基因的转录和翻译。基因扩增通常与高转录水平相关，但不一定导致蛋白质水平增加。然而，我们检测到PDGFRA、KIT和KDR编码的蛋白在GBM和GBM细胞培养中频繁表达，而不依赖于扩增状态。未来GBM患者的治疗可能包括靶向由染色体4q12段基因编码的多种激酶的药物。
A subset of glioblastomas (GBMs) carry gene amplifications on chromosomal segment 4q12. To characterize this amplicon in detail, we analyzed a set of 100 samples consisting of 65 GBMs, 10 WHO grade III astrocytomas, 12 oligodendrogliomas, and 13 glioma cell cultures. We applied multiplex ligation-dependent probe amplification to determine the gene dosage of PDGFRA, KIT, and KDR and the flanking genes USP46, RASL11B, LNX1, CHIC2, SEC3L1, and IGFBP7. The amplicon was highly variable in size and copy number and extended over a region of up to 5 Mb. Amplifications on 4q12 were observed in 15% of GBMs and 23% of GBM cell cultures but not in 22 other gliomas. We analyzed transcription and translation of some genes within this amplicon. Gene amplification generally correlated with high transcript levels but did not necessarily result in increased protein levels. However, we detected frequent expression of proteins encoded by PDGFRA, KIT, and KDR in GBMs and GBM cell cultures independent of the amplification status. Future treatment of GBM patients may include drugs targeting multiple kinases that are encoded by genes on chromosomal segment 4q12.