GENE AMPLIFICATION IN HUMAN GLIOMAS
GENE AMPLIFICATION IN HUMAN GLIOMAS
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DOI：
10.1002/glia.440150309
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发表时间：
1995-11-01
期刊：
影响因子：
6.2
通讯作者：
COLLINS, VP
中科院分区：
文献类型：
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作者：
COLLINS, VP
神经胶质瘤是成人原发性脑肿瘤中最大的一组。星形胶质细胞变异是最常见的，成人型在组织学上分为三个恶性等级。其中胶质母细胞瘤是最常见和最恶性的;它也是最好的分子遗传学和细胞遗传学研究。已知代表扩增基因的双微体染色体在50%的胶质母细胞瘤中发现。在大多数良性星形细胞瘤中未检测到扩增基因。许多基因已显示在不止一个胶质瘤病例中扩增，这些基因包括EGFR、CDK 4、SAS、MDM 2、GLI、PDGFAR、MYC、NMYC、MYCL 1、MET、GADD 153和KIT。胶质母细胞瘤中最常扩增的基因是EGFR（约40%）、CDK 4和SAS（约15%）。其余的基因以较低的频率扩增。在神经胶质瘤中最好的映射扩增子涉及12 q13 -14区域。扩增子具有未确定的大小，涵盖许多基因，并且可以重排。它发生在15%的胶质母细胞瘤中，并且几乎总是包括CDK 4和SAS基因，在约10%的肿瘤中包括MDM 2基因，并且以较低的频率包括GLI GADD 153和A2 MR。如果扩增，除了A2 MR之外的所有都过表达。扩增的EGFR基因经常重排，导致编码胞外结构域的转录本区域发生变化。所产生的受体被组成性激活。这些发现提供了现代分子生物学技术的使用对我们理解胶质瘤致癌机制产生影响的例子。(C)1995 Wiley-Liss，Inc.
Gliomas represent the largest group of primary brain tumors in adults. The astrocytic variants are the most common and the adult forms are histologically stratified into three malignancy grades. Of these glioblastoma is the most common and the most malignant; it has also been best studied by molecular genetics and cytogenetics. Double-minute chromosomes, known to represent amplified genes, are found in 50% of glioblastomas. Amplified genes are not detected in the most benign of the astrocytomas. Many genes have been shown to be amplified in more than single cases of gliomas and these include EGFR, CDK4, SAS, MDM2, GLI, PDGFAR, MYC, N MYC, MYCL1, MET, GADD153, and KIT. The most commonly amplified genes in glioblastomas are EGFR (in approximately 40%), CDK4, and SAS (in approximately 15%). The remainder of the genes are amplified at lower frequency. The best mapped amplicon in gliomas involves the 12q13-14 region. The amplicon is of undetermined size, encompasses a number of genes, and may be rearranged. It occurs in 15% of glioblastomas and almost always includes the CDK4 and SAS genes, in about 10% of tumors the MDM2 gene, and at lower frequency GLI GADD153, and A2MR. All but A2MR are overexpressed if amplified. The amplified EGFR gene is frequently rearranged, resulting in changes in the regions of the transcript that codes for the extracellular domain. The resultant receptor is constitutively activated. These findings provide examples of the impact the use of modern molecular biological techniques has had on our understanding of oncogenic mechanisms in gliomas. (C) 1995 Wiley-Liss, Inc.