Fischer U, Heckel D, Michel A, Janka M, Hulsebos T, Meese E
Department of Human Genetics, Medical School, University Hospital, Homburg/Saar, Germany.
Hum Mol Genet. 1997 Oct;6(11):1817-22. doi: 10.1093/hmg/6.11.1817.
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.
基因扩增通常被认为发生在肿瘤发展的后期，是高级别胶质瘤的一个常见特征。到目前为止，尚无关于I级星形细胞瘤基因扩增的报道。在本研究中，我们报告了一个名为胶质瘤扩增序列（GAS41）的cDNA的克隆和测序，该序列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被鉴定出来。这项技术旨在从人类肿瘤中分离扩增基因。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级星形细胞瘤中出现的频率较高。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，本研究首次证明基因扩增可发生在肿瘤发展的早期阶段。
