Hu G, Zhang W, Deisseroth A B
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Br J Haematol. 1992 Aug;81(4):489-94. doi: 10.1111/j.1365-2141.1992.tb02979.x.
A polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) assay was used to identify the exons which contained point mutations in the conserved regions (exons 4-8) of the p53 gene in 49 acute myelogenous leukaemia (AML) patients. SSCP analysis in our study was consistent with the results of subsequent direct DNA sequencing in detecting point mutational change in exons 5 and 8 of one AML patient and in exons 7 and 8 of two additional AML patients. The mutations were located at codons 245 and 273, which have been found in many other tumours, and codons 178 and 290, which have not been reported previously. All of the p53 proteins in which we detected point mutations were immunoprecipitated by the p53 monoclonal antibody PAb 240, which has been shown to recognize a mutant conformation of p53 protein. Thus, our results indicate that functional inactivation of the p53 gene by point mutational change might be one of the mechanisms underlying disease progression of AML.
采用聚合酶链反应-单链构象多态性（PCR-SSCP）分析法，对49例急性髓系白血病（AML）患者p53基因保守区（第4至8外显子）中存在点突变的外显子进行鉴定。在我们的研究中，SSCP分析结果与随后对1例AML患者第5和第8外显子以及另外2例AML患者第7和第8外显子进行直接DNA测序检测到的点突变变化结果一致。这些突变位于许多其他肿瘤中已发现的第245和273密码子，以及此前未报道过的第178和290密码子。我们检测到存在点突变的所有p53蛋白均被p53单克隆抗体PAb 240免疫沉淀，该抗体已被证明可识别p53蛋白的突变构象。因此，我们的结果表明，点突变导致p53基因功能失活可能是AML疾病进展的潜在机制之一。
