Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas.
Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas.
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发表时间：
1994-02
期刊：
影响因子：
11.2
通讯作者：
C. Cordon-Cardo;E. Latres;M. Drobnjak;M. R. Oliva;D. Pollack;J. Woodruff;V. Maréchal;Jiandong Chen;Murray F. Brennan;A. Levine
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作者：
C. Cordon-Cardo;E. Latres;M. Drobnjak;M. R. Oliva;D. Pollack;J. Woodruff;V. Maréchal;Jiandong Chen;Murray F. Brennan;A. Levine
据报道，p53和mdm2基因的遗传改变发生在软组织肉瘤中。本研究旨在确定成人软组织肉瘤中mdm2和p53基因分子异常和表达模式改变的患病率和潜在临床价值。我们分析了211例临床和病理特征良好的成人软组织肉瘤。针对mdm2和p53蛋白的单克隆抗体用于测量这些蛋白在来自这些肿瘤切片的细胞核中的过表达。207例肿瘤中有76例mdm2蛋白异常高表达，211例肿瘤中有56例p53蛋白过表达。根据与这些抗体的免疫反应性，22例mdm2和p53蛋白水平异常高。同一肿瘤中p53和mdm2蛋白的过度表达与患者的不良生存率有显著相关性（P < 0.05）。选择一组73例软组织肉瘤进行分析，使用Southern印迹，单链构象多态性，直接DNA测序，以确认mdm2基因扩增和p53突变，并将这些与免疫反应性的结果。肿瘤细胞核中p53和mdm2蛋白的过表达并不总是与mdm2基因座的基因扩增或p53基因的突变相关。这些差异的可能原因进行了讨论。
Genetic alterations in the p53 and mdm2 genes have been reported to occur in soft tissue sarcomas. This study was designed to determine the prevalence and potential clinical value of detected molecular abnormalities and altered patterns of expression of mdm2 and p53 genes in adult soft tissue sarcomas. A cohort of 211 soft tissue sarcomas from adults that were both clinically and pathologically well characterized was analyzed. Monoclonal antibodies directed against mdm2 and p53 proteins were used to measure overexpression of these proteins in the nuclei of cells from sections of these tumors. Seventy-six of 207 tumors had abnormally high levels of mdm2 proteins and 56 of 211 tumors overexpressed p53 protein. Twenty-two cases had abnormally high levels of both mdm2 and p53 proteins based upon immunoreactivity with these antibodies. There was a striking statistically significant correlation between the overexpression of p53 and mdm2 proteins in the same tumor and poor survival (P < 0.05) of the patients. A group of 73 soft tissue sarcomas was chosen for analysis using Southern blots, single strand conformation polymorphisms, and direct DNA sequencing to confirm mdm2 gene amplifications and p53 mutations and correlate these with the results of the immunoreactivities. The overexpression of p53 and mdm2 proteins in the nuclei of tumor cells did not always correlate well with gene amplification at the mdm2 locus or mutation at the p53 gene. The possible reasons for these discrepancies are discussed.