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目的:分析p53基因在中国南方部分地区家族性和早发性乳腺癌中的突变位点及特征。方法:以中国南方地区150例家族性和早发性乳腺癌患者为研究对象,提取静脉血基因组DNA,对p53基因的全部编码序列及外显子与内含子拼接区进行扩增。采用变性高效液相色谱进行预筛后,应用DNA测序分析和证实基因突变的结果。结果:150例患者中,9例的p53编码区域共发现6种不同的p53变异,其中869_888ins20(插入突变)为新发现的致病性突变,643_660del18(缺失突变)为已报道的致病性突变,91G>A,215C>G,537T>G和743G>A为已报道有致病意义的错义突变位点。此外,还发现了第4外显子区域的同义突变141G>A及第3内含子区域的缺失突变IVS3+54_70del16和9个基因多态性位点。家族性及早发性乳腺癌的p53总突变率为6.00%,其中家族性乳腺癌的p53突变率约为6.81%。早发性乳腺癌突变率约为6.25%。结论:中国南部人群家族性乳腺癌患者的p53基因胚系总突变率高于国内外文献报道,首次发现的插入突变869_888ins20的致病意义有待今后的功能学验证。缺失突变643_660del18丰富了国人p53基因突变数据库,有可能是中国乳腺癌人群的特有突变。
OBJECTIVE: To analyze the mutation sites and characteristics of p53 gene in familial and early-onset breast cancer in parts of southern China. Methods: A total of 150 cases of familial and early-onset breast cancer in southern China were enrolled in this study. Venous blood genomic DNA was extracted to amplify the entire coding sequence of p53 gene and the splicing region of exon and intron. After pre-screening by denaturing high performance liquid chromatography, DNA sequencing analysis and confirmation of gene mutation results were performed. Results: Of the 150 patients, 6 different p53 mutations were found in the p53 coding region of 9 patients. 869_888ins20 (insertional mutation) was a newly discovered pathogenic mutation and 643-660del18 (deletion mutation) was a reported pathogenic mutation , 91G> A, 215C> G, 537T> G, and 743G> A are missense mutations that have been reported to have pathogenic significance. In addition, synonymous mutations 141G> A in the exon 4 region and IVS3 + 54_70del16 and 9 polymorphic sites in the third intron region were found. The prevalence of p53 mutation in familial and early-onset breast cancer was 6.00%. The mutation rate of p53 in familial breast cancer was 6.81%. The rate of early breast cancer mutation is about 6.25%. CONCLUSIONS: The total mutation rate of p53 gene in familial breast cancer patients in southern China is higher than that reported in the literature at home and abroad. The pathogenic significance of the first inserted mutation 869_888ins20 remains to be validated in future. Missing mutation 643_660del18 enriches the Chinese p53 gene mutation database, may be unique mutations in Chinese breast cancer population.