中文摘要：

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,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。

英文摘要：

Objective： To investigate the site and characteristic ofp53 gene mutations in familial or early-onset breast cancer patients in part population of southern China. Methods： A total of 150 patients with familial and early-onset breast cancer in parts population of southern China were enrolled. Genomic DNA was isolated from each peripheral blood sample, and the entire coding sequence and exon and intron splicing region of p53 gene were amplificated by PCR in the 150 patients. The mutation analysis were detected by denaturing high performance liquid chromatography （DHPLC） and confirmed by DNA sequence analysis. Results： In the 150 patients with familial and early-onset breast cancer, 6 mutations including one novel pathogenic mutation 869_888 ins20 （insert mutation） and 5 previously reported pathogenic mutations （deletion mutation 643_660de118 and 4 missense mutation 91G〉A, 215C〉G, 537T〉G, 743G〉A） were identified in p53 gene encoding region in 9 patients of breast cancer. Moreover, one same sense mutation 141G〉A in exon 4, one 16 bases deletion in intron 3, and 9 single nucleotide polymorphisms in p53 gene introns were also identified. The total mutation frequency of p53 gene in 150 patients with familial breast cancer and early-onset breast cancer from part population of southern China was 6.00%, and the mutation frequency of familial breast cancer and early-onset breast cancer was 6.81% and 6.25%, respectively. Conclusion： The total mutation frequency of p53 gene in 150 patients with familial breast cancer and early-onset breast cancer from partpopulation of southern China is higher than the frequency previously reported. The pathogenicity of the novel mutations （insert mutation） 869_888ins20 will be confirmed by function analysis in the future study. The deletion mutation 643_660de118 enriches the p53 gene mutation database among Chinese population, which is probably the specific mutation of breast cancer in Chinese population.