【摘要】 目的研究骨肉瘤中p53基因突变及其蛋白三维结构的改变,旨在分析p53基因突变的分子机制及其与骨肉瘤发生、发展的关系。方法应用PCR-SSCP、DNA序列分析以及相关分析软件重构p53蛋白三维结构等技术对43例骨肉瘤进行研究。结果将16例p53基因突变病例分为A组(p53基因DNA结合位点发生突变或缺损组)与B组(非DNA结合位点突变组或同义突变),A组的远处转移率明显高于B组(P<0.01),组织学分化低于B组(P<0.05),且中位生存时间(10.3个月)低于B组(34.3个月)。结论 p53基因碱基的突变可引起相应氨基酸的改变,导致p53蛋白三维空间构象改变。p53基因DNA结合位点的突变可影响其蛋白的生物学功能,并促进骨肉瘤的发生、发展。更多还原

【Abstract】 Purpose To detect the mutantion of p53 gene and the 3D structure change of p53 protein in osteosarcoma,and to analyze the molecular mechanism of p53 gene and its effect in the pathogenesis and progression of osteosarcoma.Methods Reconstitution of the 3D structure of p53 protein in 43 cases of osteosarcoma was used by PCR-SSCP,DNA sequencing and analysis software.Results 16 cases with p53 gene mutation were divided into group A(mutation in p53 DNA binding loci) and group B(mutation in widely divergent p53 DNA or synonymous mutation).The distant metastasis rate in group A was significant higher than that in group B(P<0.01).The differentiation degree of the tumor in group A was lower than that in group B(P<0.05) and the median survival time in group A(10.3 months) was shorter than that in group B(34.3 months)(P<0.05).Conclusion The mutation of p53 gene may induce the change of the corresponding amino acid and lead to the alteration of the 3D structure of p53 protein,which can influence the biological function of p53 protein and promote the occurrence and development of osteosarcoma.更多还原