Analysis of mdm2 and p53 gene alterations in glioblastomas and its correlation with clinical factors
Analysis of mdm2 and p53 gene alterations in glioblastomas and its correlation with clinical factors
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DOI：
10.1023/a:1006410702284
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发表时间：
2000-09-01
影响因子：
3.9
通讯作者：
Bamberg, M
中科院分区：
文献类型：
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作者：
Schiebe, M;Ohneseit, P;Bamberg, M
恶性胶质瘤是最常见的原发性脑肿瘤。最近的研究定义了几个遗传标记，这可能表征胶质母细胞瘤的分子生物学亚群，可能具有预后意义。为了阐明恶性胶质瘤肿瘤发生中鼠双微体（mdm）2基因扩增和抑癌基因p53突变的参与，我们分析了一系列75例胶质母细胞瘤。三分之一的胶质母细胞瘤中存在p53突变，13%的胶质母细胞瘤中存在mdm2扩增。结果发现p53基因第156位密码子存在一个热点突变，4例肿瘤组织中也发现了相同的点突变。mdm2扩增的肿瘤中没有p53突变，支持mdm2扩增是p53失活的替代机制的假设。p53突变肿瘤患者明显年轻，平均年龄为44岁。此外，可以检测到该亚组患者的总生存期较长。在我们的研究中，生存评估显示mdm2基因扩增与较短的生存时间显著相关，并支持mdm2癌基因激活似乎发生在肿瘤进展的晚期，可能是阴性预后标志物的特征。
Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with probably prognostic implications. To elucidate the involvement of murine-double-minute (mdm)2 gene amplifications and mutations of the tumor suppressor gene p53 in the tumorigenesis of malignant gliomas we analyzed a series of 75 glioblastomas. The p53 mutations occur in one-third of glioblastomas, mdm2 amplifications were found in 13% of cases. Our analysis revealed a hot spot in the p53 gene locus in codon 156, the same point mutation was detected in 4 tumor samples. None of the mdm2 amplified tumors had p53 mutations, supporting the hypothesis, that mdm2 amplifications are alternative mechanisms for p53 inactivation. Patients with p53 mutated tumors were significantly younger characterized by a mean age of 44 years. Additionally association with longer overall survival could be detected for this subgroup of patients. In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker.