Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I

Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I
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DOI:
10.1093/hmg/6.11.1817
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发表时间:
1997-10-01
影响因子:
3.5
通讯作者:
Meese, E
Meese, E
中科院分区:
生物学2区
文献类型:
--
作者:
Fischer, U;Heckel, D;Meese, E

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基因扩增通常被认为发生在肿瘤发展的晚期,是高级别胶质瘤的一个常见特征。到目前为止,还没有关于I级星形细胞瘤发生扩增的报道。在这项研究中,我们报道了一种被称为胶质瘤扩增序列(GAS41)的cDNA的克隆和测序。该序列是最近通过显微切割介导的cDNA捕获技术在一个胶质母细胞瘤细胞系中鉴定出来的。这种技术是专门用于从人类肿瘤中分离扩增基因的。在多形性胶质母细胞瘤和III级星形细胞瘤中发现GAS41的拷贝数增加,在I级和II级星形细胞瘤中也有较高频率的增加。序列比较表明GAS41蛋白与酵母和人类的AF - 9以及人类的ENL蛋白具有高度同源性。AF - 9和ENL都属于一类新的转录因子,这表明GAS41可能也代表一种转录因子。由于GAS41是在低级别胶质瘤中发现的第一个拷贝数增加的基因,这项研究首次提供了基因扩增可以发生在肿瘤发展早期的证据。
Gene amplification, which is generally considered to occur late in tumor development, is a common feature of high grade glioma. Up until now, there have been no reports on amplification in astrocytoma grade I. In this study, we report cloning and sequencing of a cDNA termed glioma-amplified sequence (GAS41) which was identified recently in a glioblastoma cell line by microdissection-mediated cDNA capture. This technique is tailored to isolate amplified genes from human tumors. An increased copy number of GAS41 was found in glioblastoma multiforme and astrocytoma III, and at a high frequency in astrocytoma grades I and II. Sequence comparison indicates a high homology between the GAS41 protein, the yeast and human AF-9 and the human ENL proteins. Both AF-9 and ENL belong to a new class of transcription factors, indicating that GAS41 might also represent a transcription factor. With GAS41 being the first gene found with increased copy number in low grade glioma, this study provides the first evidence that gene amplification can occur in early tumor development.