首页 | 本学科首页   官方微博 | 高级检索  
     

中国上海家族性乳腺癌BRCA1和BRCA2基因的突变
引用本文:宋传贵,胡震,袁文涛,狄根红,沈镇宙,黄薇,邵志敏. 中国上海家族性乳腺癌BRCA1和BRCA2基因的突变[J]. 中华医学遗传学杂志, 2006, 23(1): 27-31
作者姓名:宋传贵  胡震  袁文涛  狄根红  沈镇宙  黄薇  邵志敏
作者单位:1. 200032,上海,复旦大学附属肿瘤医院乳腺科,复旦大学乳腺癌/肿瘤研究所,复旦大学上海医学院肿瘤学系;福建医科大学附属协和医院肿瘤科
2. 200032,上海,复旦大学附属肿瘤医院乳腺科,复旦大学乳腺癌/肿瘤研究所,复旦大学上海医学院肿瘤学系
3. 国家人类基因组南方研究中心
基金项目:国家自然科学基金(30371580);国家“十五”攻关项目(2002AA711A08);上海市科委重点项目(03JC14019);复旦大学研究生创新基金
摘    要:目的研究上海地区家族性乳腺癌中BRCA1/BRCA2基因的突变位点及携带情况。方法研究对象来自35个汉族家族性乳腺癌家系,家系中至少有一个一级亲属乳腺癌患病史。共35例患者,其中13例发病年龄≤加岁。由静脉血提取基因组DNA,对BRCA1/BRCA2基因的全部编码序列进行扩增。扩增产物突变分析先由变性高效液相色谱分析进行筛查,之后进行DNA直接测序证实。结果在BRCA1基因中发现有4个突变位点,其中2个为新发现位点——拼接点突变(IVS17-1G〉T;IVS21+1G〉C);另两个为已报道的致病突变位点——移码突变(1100delAT;5640delA)。BRCA2基因的1个致病突变位点位于11号外显子上,为移码突变(5802delAATT)。另外,共发现有12个新的单核苷重复多态位点,都未引起氨基酸编码改变;其中,8个在BRCA1基因上,4个在BRCA2基因上。在家族性乳腺癌中,BRCA1突变频率(11.4%)高于BRCA2基因(2.9%)。结论新发现的2个BRCA1基因的拼接点突变可能是中国上海人群家族性乳腺癌的特有突变位点;在我国上海地区人群中,BRCA1基因突变起着比BRCA2基因更大的作用;该研究丰富了中国人群中BRCA基因的突变谱,并为未来的临床基因检测提供了筛查模式。

关 键 词:乳腺肿瘤 BRCA1基因 BRCA2基因 基因突变
收稿时间:2005-09-02
修稿时间:2005-09-02

BRCA1 and BRCA2 gene mutations of familial breast cancer from Shanghai in China
SONG Chuan-gui,HU Zhen,YUAN Wen-tao,DI Gen-hong,SHEN Zhen-zhou,HUANG Wei,SHAO Zhi-min. BRCA1 and BRCA2 gene mutations of familial breast cancer from Shanghai in China[J]. Chinese journal of medical genetics, 2006, 23(1): 27-31
Authors:SONG Chuan-gui  HU Zhen  YUAN Wen-tao  DI Gen-hong  SHEN Zhen-zhou  HUANG Wei  SHAO Zhi-min
Affiliation:1. Breast Cancer Institute, Cancer Hospital/Cancer Institute; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 P. R. China; 2.Department of Oncology , Affdiated Union Hospital, Fujian Medical University, Fuzhou , Fujian, 350001 P. R. China; 3.Chinese National Human Genome Center at Shanghai, Shanghai, 201203 P. R. China
Abstract:OBJECTIVE: To investigate the prevalence of BRCA1 and BRCA2 gene mutations among breast cancer patients with affected relatives in Shanghai of China. METHODS: Thirty-five breast cancer patients who had at least one first-degree relative affected were analyzed, among whom 13 patients suffered from breast cancer at age of less than 40 years. A comprehensive BRCA1 and BRCA2 mutation analysis was performed through denaturing high-performance liquid chromatography (DHPLC) and subsequent DNA direct sequencing. RESULTS: Four mutations in BRCA1 gene, including 2 novel splice-site mutations (IVS17-1G>T, IVS21+1G>C) and 2 frameshift mutations (1100delAT; 5640delA) were identified. One frameshift mutation (5802delAATT) was detected in exon 11 of BRCA2. Additional 12 novel single nucleotide polymorphisms(SNPs) were detected, including a novel unclassified variant and 7 novel intronic variants in BRCA1, and 4 novel intronic variants in BRCA2, with which all caused no alteration of amino acid coding. The mutation frequency of BRCA1 and BRCA2 in patients with family history was 11.4% and 2.9%, respectively. CONCLUSION: Two novel mutations in BRCA1 may be mutations characterized to familial breast cancer of Chinese Shanghai population. The BRCA2 may contribute to mutation less than BRCA1 in familial breast cancer. Our data contribute to information on mutation spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing policy in China.
Keywords:breast cancer   BRCA1 gene   BRCA2 gene   mutation
本文献已被 维普 万方数据 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号