中国南部人群家族性及早发性乳腺癌患者p53基因胚系突变分析

发布时间：2018-04-01 07:35

本文选题：乳腺癌　切入点：p基因　出处：《中南大学学报(医学版)》2017年05期

【摘要】：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,91GA,215CG,537TG和743GA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141GA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。
[Abstract]:Objective: to analyze the mutation loci and characteristics of p53 gene in familial and early onset breast cancer in southern China.Methods: a total of 150 patients with familial and early onset breast cancer in southern China were studied. Genomic DNA was extracted from venous blood to amplify the whole coding sequence of p53 gene and the splicing region between exon and intron.After screening by denaturing high performance liquid chromatography (DHPLC), the results of gene mutation were analyzed and confirmed by DNA sequencing.Results in 9 out of 150 patients, 6 different p53 variants were found in p53 coding region.Among them, 869888ins20 (insertion mutation) was a newly discovered pathogenicity mutation 643D 660del18 (deletion mutation). It was reported that the pathogenicity mutation was 91GA 215CGN 537TG and 743GA were reported missense mutation sites.In addition, synonymous mutant 141GA in exon 4 and deletion mutation in intron 3, IVS3 54_70del16, and 9 polymorphic loci were also found.The total mutation rate of p53 in familial early onset breast cancer was 6.00, and the mutation rate of p53 in familial breast cancer was about 6.81.The mutation rate of early onset breast cancer was about 6.25%.Conclusion: the total mutation rate of p53 blastocyst in familial breast cancer patients in southern China is higher than that reported in domestic and foreign literatures. The pathogenicity of the first insertion mutation 869_888ins20 remains to be verified in the future.Deletion mutation 643_660del18 enriches Chinese p53 gene mutation database and may be a unique mutation in Chinese breast cancer population.
【作者单位】：中南大学湘雅医院乳腺外科;四川省肿瘤医院乳腺外科;
【基金】：国家自然科学基金(81372842/H1622) 国家青年科学基金(81001179/RI622) 湖南省科学技术厅科技计划一般项目(08FJ3174)~~
【分类号】：R737.9

【相似文献】