Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets.
Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets.
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发表时间：
1996-11
期刊：
影响因子：
11.2
通讯作者：
G. Reifenberger;Koichi Ichimura;J. Reifenberger;Elkahloun Ag;Meltzer Ps;V. Collins
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作者：
G. Reifenberger;Koichi Ichimura;J. Reifenberger;Elkahloun Ag;Meltzer Ps;V. Collins
我们以前曾报道过大约15%的间变性星形细胞瘤和胶质母细胞瘤表现出染色体12q13-q15区段的一个或多个基因的扩增和过表达（G. Reifenberger等人，癌症研究所，54，4299 - 4303，1994）。最常扩增和过表达的基因是CDK4（与SAS共扩增）和MDM2。由于个别恶性胶质瘤显示CDK4/SAS扩增，但没有MDM2扩增，反之亦然，因此可能存在位于CDK4和MDM2之间的共同扩增靶基因。我们已经解决了这个问题，通过执行一系列的24个原发性恶性胶质瘤和两个胶质母细胞瘤细胞系12q13-q15扩增的详细扩增子映射。所有肿瘤和细胞系在12q13-q15的8个基因位点和6个匿名位点进行分析，包括位于CDK4和MDM2之间的7个位点。这些研究揭示了两个扩增中心，一个在CDK4/SAS，另一个在MDM 2。发现位于MDM2或CDK4/SAS附近的许多基因座，包括基因GADD 153、GLI、RAP 1B、A2 MR和IFNG，在一些肿瘤中共扩增，但不一致地过表达。所有扩增子在CDK4/SAS和MDM2之间是不连续的。因此，我们的研究结果排除了CDK4/SAS和MDM2之间的共同扩增靶点，并提供了额外的证据，表明这些基因代表了两个独立的选择靶点。
We have reported previously that about 15% of anaplastic astrocytomas and glioblastomas show amplification and overexpression of one or more genes from chromosomal segment 12q13-q15 (G. Reifenberger et al., Cancer Res., 54, 4299-4303, 1994). The genes most frequently amplified and overexpressed were CDK4 (with coamplification of SAS) and MDM2. Because individual malignant gliomas showed CDK4/SAS amplification but no MDM2 amplification and vice versa, the possibility remained of a common amplification target gene located between CDK4 and MDM2. We have addressed this question by performing a detailed amplicon mapping of a series of 24 primary malignant gliomas and two glioblastoma cell lines with 12q13-q15 amplification. All tumors and cell lines were analyzed at eight gene loci and six anonymous loci from 12q13-q15, including seven loci located between CDK4 and MDM2. These studies revealed two centers of amplification, one at CDK4/SAS and the other at MDM2. A number of loci located close to either MDM2 or CDK4/SAS, including the genes GADD153, GLI, RAP1B, A2MR, and IFNG, were found to be coamplified in some tumors but not overexpressed consistently. All amplicons were discontinuous between CDK4/SAS and MDM2. Our results thus exclude a common amplification target between CDK4/SAS and MDM2 and provide additional evidence that these genes represent two independent targets of selection.