肺癌p53基因突变与蛋白表达关系的研究  

Correlation between p53 gene mutation and protein expression in 30 cases of human lung cancer

作　　者：张骏[1] 郑杰[1] 方伟岗[1] 王洁良[1] 由江峰[1] 崔湘琳[1] 吴秉铨[1] 

机构地区：[1]北京医科大学基础医学院病理学系

出　　处：《中华医学杂志》1998年第11期846-849,共4页National Medical Journal of China

摘　　要：目的以测序结果为标准，探讨免疫组织化学和聚合酶链反应单链构象多态性（ＰＣＲＳＳＣＰ）两种方法用于检测肺癌ｐ５３基因突变的敏感性及优缺点。方法用免疫组织化学、ＰＣＲＳＳＣＰ和ＰＣＲ产物直接测序检查３０例肺癌标本的Ｐ５３蛋白和基因改变。结果３０例肺癌标本经测序共检出２２例突变，突变位于第５外显子８例（３６％）；位于第６外显子２例（９％）；位于第７外显子７例（３２％）；位于第８外显子５例（２３％）。其中错义突变１４例（６４％）；同义突变４例（１８％）；移码突变３例（１４％）；剪切部位突变１例（５％）。Ｇ：Ｃ→Ｔ：Ａ颠换突变占总突变数的４１％（９／２２）。在免疫组化检测强阳性同时ＰＣＲＳＳＣＰ检测阳性的１０例肺癌中均检出了ｐ５３错义突变；在免疫组化检测阴性而ＰＣＲＳＳＣＰ检测阳性的１０例肺癌中，９例被检出ｐ５３突变。其中４例是同义突变、２例缺失突变、１例错义突变、１例插入突变、１例剪切部位突变；在免疫组织化学检测阳性、ＰＣＲＳＳＣＰ检测阴性的１０例肺癌中仅检出３例错义突变，其余７例肺癌的ｐ５３基因第５～８外显子均为野生型。结论肺癌ｐ５３基因突变多位于第５和第７外显子，以错义突变为主，Ｇ：Ｃ→Ｔ：Ａ颠换突?Objective To investigate the correlation between p53 gene mutation and protein expression and discuss the sensitivities of immunohistochemistry and PCR SSCP in detecting p53 abnormalities in lung cancer. Methods Immunohistochemistry, PCR SSCP, and PCR sequencing were used. Results 22 of 30 patients showed p53 mutations by PCR sequencing. Mutations of 8 patients (36%) located on exon 5, 2(9%) on exon 6, 7 (32%) on exon 7, and 5(23%) on exon 8, respectively. 14 patients (64%) showed missense mutations, and 4(18%) neutral mutations, 3(14%) frameshifts and 1(5%) splice site mutation. In all mutations, G:C→T:A transversions accounted for 41%(9/22). p53 missense mutations were found in all 10 patients whose immunohistochemistry and PCR SSCP were both positive. Nine of 10 patients whose PCR SSCP was positive but immunohistochemistry negative had p53 mutations, including 4 patients with neutral mutations, 3 frameshift mutations, 1 missense mutation, and 1 splice site mutation. In 10 patients whose immunohistochemistry was positive but PCR SSCP negative, only 3 showed p53 missense mutations. Conclusion Most of p53 mutation sites located on exon 5 and exon 7 in lung cancer of China. Missense mutations and G to T transversions were prevalent. If both PCR SSCP and immunohistochemistry gave the positive results, p53 missense mutations may be expected.

关 键 词：肺肿瘤 基因表达 基因突变 P53基因 

分 类 号：R734.2[医药卫生—肿瘤]