Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations.
Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations.
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发表时间：
1993-06
期刊：
影响因子：
11.2
通讯作者：
G. Reifenberger;Lu Liu;K. Ichimura;Schmidt Ee;V. Collins
中科院分区：
文献类型：
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作者：
G. Reifenberger;Lu Liu;K. Ichimura;Schmidt Ee;V. Collins
MDM 2（鼠双微体2）基因最近被证明编码一种细胞蛋白，该蛋白可以复合p53肿瘤抑制基因产物并抑制其功能。我们研究了一系列的157原发性脑肿瘤，并在这里报告，MDM 2基因扩增和过表达的胶质母细胞瘤和间变性星形细胞瘤的8-10%。因此，在这些肿瘤类型中，MDM 2代表了继表皮生长因子受体基因之后第二最频繁扩增的基因。在MDM 2扩增的情况下，p53转录物的测序显示没有突变，限制性片段长度多态性分析显示，除了一个例外，17号染色体上没有等位基因的损失。我们的研究结果表明，MDM 2的扩增和过表达可能是一个替代的分子机制，其中一个子集的人类恶性胶质瘤逃脱p53调控的生长控制。
The MDM2 (murine double minute 2) gene has recently been shown to code for a cellular protein that can complex the p53 tumor suppressor gene product and inhibit its function. We studied a series of 157 primary brain tumors and report here that the MDM2 gene is amplified and overexpressed in 8-10% of glioblastomas and anaplastic astrocytomas. Thus, MDM2 represents the second most frequently amplified gene after the epidermal growth factor receptor gene in these tumor types. Sequencing of the p53 transcripts in the cases with MDM2 amplification revealed no mutations and restriction fragment length polymorphism analysis showed, with one exception, no losses of alleles on chromosome 17. Our results indicate that amplification and overexpression of MDM2 may be an alternative molecular mechanism by which a subset of human malignant gliomas escapes from p53-regulated growth control.