中文摘要：

目的：探讨中国湖南人群家族性和早发性乳腺癌患者磷酸酶张力蛋白同源物基因（phosphatase and tensin homolog,PTEN）和Nijmegen断裂综合征1（Nijmegen breakage syndrome 1,NBS1）基因的突变特点及潜在意义。方法：纳入131例家族性和早发性乳腺癌患者,采用变性高效液相色谱法（denaturing high performance liquid chromatography,DHPLC）对PTEN基因所有外显子以及NBS1基因外显子5和外显子6的突变位点进行筛查,然后采用DNA直接测序证实。结果：在131例患者中,有2例发生PTEN基因插入突变IVS4＋109ins TCTTA,其突变频率为1.15%;首次发现PTEN基因的2个突变225 A〉C（h r 160 Pro）与IVS5＋13T〉C,另一个已报道的错义突变为rs121909229 G〉A（Arg 130 Gln）。在NBS1基因上发现3个突变,其中IVS6＋43A〉G与IVS6＋127A〉G为首次发现,另一个已报道的同义突变为rs1805794G〉C（Glu 185 Gln）。结论：新发现的PTEN和NBS1突变可能是中国湖南人群家族性和早发性乳腺癌的特有突变位点。

英文摘要：

Objective： To investigate the profile and potential significance of PTEN and NBS1 mutations among patients with familial or at early onset breast cancer in Hunan province.Methods： A total of 131 breast cancer patients with familial history or suff ered from breast cancer at the age of less than 35 years old were included in this study. A comprehensive phosphatase and tensin homolog（PTEN） and nibrin（NBS1） mutation analysis was performed through denaturing high performance liquid chromatography（DHPLC） and subsequent DNA direct sequencing.Results： Among 131 patients, a reported mutation IVS4＋109insTCTTA in PTEN gene were identified in two patients. The mutation frequency of IVS4＋109insTCTTA was 1.15%. Two mutations in PTEN gene, 225 AC（Thr 160 Pro） and IVS5＋13TC, was firstly discovered.Another reported missense mutation was rs121909229 GA（Arg 130 Gln）. Th ree mutations were detected in NBS1 gene, of which IVS6＋43AG and IVS6＋127AG were firstly discovered and another reported synonymous mutations was rs1805794 GC（Glu 185 Gln）.Conclusion： The novel mutations in PTEN and NBS1 might be specific to the familial and earlyonset breast cancer of Chinese Hunan population.