74例早发性乳腺癌患者BRCA1和BRCA2基因致病突变研究  

BRCA1 and BRCA2 pathogenic mutations in 74 patients with early-onset breast cancer

作　　者：杨柳春[1,2] 刘晓静[2] 靳彦文[3] 进淑娟[2] 韩小伟[2] 庞汉民[2] 李建鹏[2] 孟迪[2] 左思[2] 公彦栋 曹诚[3] 黄焰[1,2] 

机构地区：[1]安徽医科大学解放军307临床学院,北京100071 [2]军事医学科学院附属医院乳腺外科,北京100071 [3]军事医学科学院生物工程研究所,北京100850

出　　处：《军事医学》2017年第5期398-401,共4页Military Medical Sciences

基　　金：中国健康促进基金;军事医学科学院创新基金资助项目(2013ZHYX012)

摘　　要：目的研究乳腺癌易感基因BRCA1和BRCA2在早发性乳腺癌(确诊年龄≤35岁)患者中突变情况,分析致病突变与临床特征之间关系。方法选择2014年9月至2016年6月期间就诊于军事医学科学院附属医院的早发性乳腺癌患者74例,采用高通量二代测序技术以及生物信息分析,对纳入患者BRCA1和BRCA2基因的49个外显子序列及拼接区序列进行检测分析,并将患者按临床特征分组,X^2检验比较BRCA1和BRCA2致病突变在各组的分布。结果在74例早发性乳腺癌患者中,检测到15例(20.27%)BRCA1/2致病突变,包括5例(6.76%)BRCA1致病突变,10例(13.51%)BRCA2致病突变。其中11例为新发现致病突变,检测到1例患者携带相对高频致病基因突变BRCA1∶c.5470_5477delTGCCCAAT。有乳腺癌或卵巢癌家族史组携带致病突变率明显高于无家族史组(40.91%vs 11.54%,X^2=6.534,P=0.011)。结论 BRCA1/2致病突变对早发性乳腺癌意义重大,尤其是伴有乳腺癌或卵巢癌家族史的早发性乳腺癌。新发现的致病突变可能为中国人群特有突变。BRCA1∶c.5470_5477delTGCCCAAT可能成为中国人群的始祖突变。Objective To investigate the pathogenic mutations of BRCA1 and BRCA2 in patients with early-onset breast cancer（ ≤35 years） and explore the relationships between BRCA1/2 mutations and clinical features. Methods Seventy-four patients with early-onset breast cancer were enrolled, who were treated in Hospital 307 between September 2014 and June 2016. High-throughput sequencing was used to test the 49 exon sequences and adjacent sequences of BRCA1 and BRCA2. χ2 test was used to analyze the distribution of BRCA1/2 pathogenic mutations in each group that was set up according to clinical features. Results Fifteen mutations（20.27% ） were identified, including 5（6.76% ） in BRCA1 and 10 （ 13.51% ） in BRCA2. Eleven new pathogenic mutations were discovered, and BRCA1 ： c. 5470_5477delTGCCCAAT was found in one patient. The frequency of BRCA1/2 mutations in the group with a family history of breast cancer or ovarian cancer was higher than in the group without a family history （40.91% vs 11. 54% ） （Z2 = 6. 534, P = 0. 011 ）. Conclusion BRCA1/2 pathogenic mutation is significant for early-onset breast cancer, especially for those with a family history of breast or ovarian cancer. The new mutations may be specific to Chinese people. BRCA1 ： c. 5470_ 5477delTGCCCAAT may be the ancestor mutation among the Chinese.

关 键 词：乳腺肿瘤 乳腺癌易感基因1 乳腺癌易感基因2 突变 

分 类 号：R737.9[医药卫生—肿瘤]