眼眶横纹肌肉瘤N-ras癌基因点突变及rasp21、p53蛋白的异常表达

Point mutations of N-ras oncogene and abnormal expression of rasp21, p53 proteins in orbital rhabdomyosarcoma

目的 研究眼眶横纹肌肉瘤 (rhabdomyosarcoma ,RMS )N ras癌基因点突变、rasp2 1、p5 3蛋白的异常表达 ,探讨基因突变在眼眶RMS发病中的作用。方法 应用特异性高突变区位不同的突变型寡核苷酸探针及突变型rasp2 1、p5 3单克隆抗体 ,对 2 1例眼眶RMS组织进行DNA斑点杂交和免疫组织化学分析。结果 4例眼眶RMS细胞中发生N ras癌基因 12密码子第 2个碱基突变 ,5例眼眶RMS组织中发生 6 1密码子第 3个碱基突变 ,其中 2例同时有 2个密码子碱基突变。免疫组织化学检测 ,rasp2 1及p5 3蛋白阳性表达增强者分别为 9例和 16例 ,rasp2 1、p5 3蛋白阳性表达增强者其预后较无异常表达者差。结论 眼眶RMS组织中癌基因ras和抑癌基因p5 3突变 。

Objective The point mutations of N ras oncogene and the abnormal expression of rasp21 and p53 proteins in orbital rhabdomyosarcoma (RMS) were analyzed in order to explore the role of oncogene mutations in the pathogenesis of orbital RMS and its relation to patients′ prognosis Method 21 human orbital RMS tissues were analyzed by dot blot hybridization and immunohistochemistry using synthetic specific oligonucleotide probes and mutant rasp21, p53 monoclonal antibodies Results The second base mutation of codon 12 of the N ras oncogene was found in 4 patients The third base mutation of codon 61 was found in 5 patients The mutant rate was 33 3% By immunohistochemistry analysis, the overexpression of rasp21 and p53 protein level was found in 42 9% and 76 2% respectively The prognosis of patients with overexpression of ras p21, p53 was worse than that of normal expression ( P <0 01) Conclusion The mutants of ras and p53 oncogene play important roles in the pathogenesis of orbital RMS, and the abnormal expression of their protein products is related to patients′ prognosis