Rubio M P, von Deimling A, Yandell D W, Wiestler O D, Gusella J F, Louis D N
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown 02129.
Cancer Res. 1993 Aug 1;53(15):3465-7.
We have previously described 10 astrocytomas with accumulation of p53 protein but no mutations in p53 exons 5-8, and we have suggested that they might represent overexpression of wild type protein or mutations in less conserved regions of the gene. To investigate these possibilities further, we studied the tumors with immunohistochemistry for wild type and mutant p53 protein and showed that all cases stained with the wild type PAb 1801 antibody but only one case stained with the mutant-specific PAb 240 antibody. To support the hypothesis that the accumulated p53 protein is wild type in most cases, we used single-strand conformation polymorphism analysis and DNA sequencing to evaluate p53 exons 4, 9, and 10 and did not detect mutations at these loci. Although the product of the MDM2 oncogene binds wild type p53 and may account for p53 accumulation, slot-blot analysis of these astrocytomas did not detect MDM2 gene amplification. Thus, evidence suggests that some astrocytomas may accumulate wild type p53 protein but not as a result of MDM2 gene amplification. Furthermore, PAb 1801 immunohistochemistry may not be an adequate method of screening astrocytomas for p53 mutations.
我们之前描述过10例p53蛋白聚集但p53基因外显子5 - 8无突变的星形细胞瘤，我们曾提出它们可能代表野生型蛋白的过表达或该基因较不保守区域的突变。为进一步研究这些可能性，我们用免疫组织化学方法研究了这些肿瘤的野生型和突变型p53蛋白，结果显示所有病例均被野生型PAb 1801抗体染色，但只有1例被突变特异性PAb 240抗体染色。为支持大多数病例中积累的p53蛋白为野生型这一假说，我们用单链构象多态性分析和DNA测序评估p53基因外显子4、9和10，未在这些位点检测到突变。尽管MDM2癌基因产物可结合野生型p53并可能解释p53的积累，但对这些星形细胞瘤的狭缝杂交分析未检测到MDM2基因扩增。因此，有证据表明一些星形细胞瘤可能积累野生型p53蛋白，但并非MDM2基因扩增所致。此外，PAb 1801免疫组织化学可能不是筛查星形细胞瘤p53突变的合适方法。
