Litofsky N S, Hinton D, Raffel C
Division of Neurosurgery, University of Massachusetts Medical Center, Worcester.
Neurosurgery. 1994 Jun;34(6):967-72; discussion 972-3. doi: 10.1227/00006123-199406000-00003.
Mutations in the p53 gene, which codes for a cell division regulatory protein, have been identified in approximately one-third of adult astrocytomas. We evaluated 35 astrocytic tumors (17 pilocytic, 4 diffuse low grade, 12 anaplastic, and 2 glioblastoma) in pediatric patients for p53 mutations, using polymerase chain reaction-single-stranded conformation polymorphism analysis as a screening technique. Additionally, those tumors identified with homozygosity in the area of the p53 gene on chromosome 17 by Southern blotting were sequenced to look for p53 mutations. No tumors were identified with polymerase chain reaction-single-stranded conformation polymorphism analysis shifts indicative of mutations in the p53 gene. Five of 21 tumors were homozygous in the region of the p53 gene on chromosome 17; no mutations in exons 5 to 8 were found in any of these tumors. The frequency of p53 mutation in pediatric astrocytomas is significantly less than the frequency for adult tumors, regardless of tumor grade. Furthermore, the frequency of p53 mutations in high-grade astrocytomas is significantly lower in pediatric tumors than in adult tumors. These results suggest that p53 is not important in the oncogenesis of pediatric astrocytomas. Oncogenesis in pediatric astrocytomas may occur by different mechanisms than those of similar tumors in adults.
p53基因编码一种细胞分裂调节蛋白，在大约三分之一的成人星形细胞瘤中已发现该基因发生突变。我们采用聚合酶链反应-单链构象多态性分析作为筛查技术，评估了35例儿科患者的星形细胞肿瘤（17例毛细胞型、4例弥漫性低级别、12例间变性和2例胶质母细胞瘤）是否存在p53突变。此外，对那些通过Southern印迹法在17号染色体p53基因区域检测到纯合性的肿瘤进行测序，以寻找p53突变。聚合酶链反应-单链构象多态性分析未发现有p53基因突变指示性条带迁移的肿瘤。21例肿瘤中有5例在17号染色体p53基因区域呈纯合性；这些肿瘤中均未发现外显子5至8有突变。无论肿瘤级别如何，儿科星形细胞瘤中p53突变的频率均显著低于成人肿瘤。此外，儿科高级别星形细胞瘤中p53突变的频率显著低于成人肿瘤。这些结果表明，p53在儿科星形细胞瘤的肿瘤发生过程中并不重要。儿科星形细胞瘤的肿瘤发生机制可能与成人相似肿瘤的机制不同。
