Alterations of the TP53 gene in human gliomas.
Alterations of the TP53 gene in human gliomas.
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发表时间：
1994-03
期刊：
影响因子：
11.2
通讯作者：
B. Rasheed;R. McLendon;J. Herndon;H. Friedman;A. Friedman;D. Bigner;S. Bigner
中科院分区：
文献类型：
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作者：
B. Rasheed;R. McLendon;J. Herndon;H. Friedman;A. Friedman;D. Bigner;S. Bigner
分析了72例成人和48例儿童的所有级别和组织学类型的胶质瘤的TP 53基因突变、17 p杂合性丢失（洛）和TP 53蛋白积累，以确定不同组织学类型的肿瘤之间以及成人和儿童肿瘤之间TP 53改变的发生率和类型是否不同。还对这些肿瘤进行了10号染色体的洛缺失和表皮生长因子受体、C-MYC、N-MYC、GLI、血小板衍生生长因子受体-α和鼠双微体2基因扩增的评价，以确定这些肿瘤进展中涉及的分子改变模式。120个肿瘤中有17个含有TP 53基因突变。其中一例TP 53基因突变的肿瘤来自48例年龄小于18岁的患者。17例突变肿瘤中有12例发生在18-45岁年龄组的27例患者中，而4例突变肿瘤发生在45岁以上的45例患者中。在间变性星形细胞瘤患者中TP 53突变的发生率也增加。然而，没有观察到TP 53突变的存在与患者生存之间的显著关联。这些研究表明，TP 53基因突变是18-45岁年龄组神经胶质细胞肿瘤的常见机制，但与进展和晚期组织学分级无关。然而，多形性胶质母细胞瘤10号染色体洛和基因扩增分别发生在82%和40%，无论是单独观察还是与TP 53基因改变沿着观察，都与肿瘤的晚期组织学分级相关。相反，在儿童胶质瘤中，TP 53基因改变、17 p和10 q的洛以及基因扩增在所有级别的肿瘤中都是罕见的，这表明目前未知的机制是这些肿瘤发生和发展的原因。
Glial tumors of all grades and histological types from 72 adults and 48 children were analyzed for mutations of the TP53 gene, loss of heterozygosity (LOH) for 17p, and accumulation of TP53 protein to determine whether the incidence and type of TP53 alterations differ among tumors of different histological type and between tumors from adults and children. These tumors were also evaluated for LOH for chromosome 10 and for amplification of the epidermal growth factor receptor, C-MYC, N-MYC, GLI, platelet-derived growth factor receptor-alpha, and murine double minute 2 genes to determine the patterns of molecular alterations involved in the progression of these neoplasms. Seventeen of the 120 tumors contained mutations of the TP53 gene. One of the tumors with TP53 gene mutation was from one of the 48 patients less than 18 years of age. Twelve of the 17 tumors with mutations occurred among the 27 patients in the 18-45-year age group, while 4 tumors with mutations were among the 45 patients more than 45 years old. There was also an increased incidence of TP53 mutation in patients with anaplastic astrocytoma histology. However, no significant association between presence of TP53 mutation and patient survival was observed. These studies demonstrate that TP53 gene mutations are a common mechanism for glial cell neoplasms in the 18-45-year age group but are unrelated to progression and advanced histological grade. LOH for chromosome 10 and gene amplification, however, occurring in 82 and 40%, respectively, of glioblastoma multiforme, whether seen alone or along with TP53 gene alterations, are related to advanced histological grade of the tumor. In childhood gliomas, in contrast, TP53 gene alterations, LOH for 17p and 10q, and gene amplification are uncommon in tumors of all grades, suggesting that presently unknown mechanisms are responsible for the genesis and progression of these tumors.