中国人群特有的BRCA1/2基因内含子突变对BRCA1/2功能的影响及与乳腺癌发病的相关性分析

BRCA1/2基因是与家族性乳腺癌关系最为密切的两个基因。在中国家族性乳腺癌中BRCA1/2基因的致病性突变为10%。除此之外，BRCA1/2基因中还存在大量的功能不明突变，主要包括错义突变和内含子突变。目前研究主要集中在错义突变对BRCA1/2功能的影响，而很少关注BRCA1/2基因的内含子突变。BRCA1/2基因的内含子突变对BRCA1/2功能的影响已成为该领域最为棘手的难题。在本课题组的前期工作中，我们完成了409例中国家族性乳腺癌BRCA1和BRCA2基因全编码序列的检测，发现了20例中国人群特有的BRCA1/2基因内含子突变。本研究将采用生物信息学、功能学实验及临床表型相结合的策略，分析这些突变对BRCA1/2功能的影响，探索这些突变与乳腺癌发生的相关性。研究结果不仅可以拓宽我们对内含子功能的新认识，更为重要的是将直接影响突变携带者治疗方案的选择和预后的判断，具有重要的临床意义。

Breast cancer susceptibility genes, BACA1/2, are associated with the development of familial breast cancer.The BRCA1/2 mutation rate in Chinese breast cancer families is 10%. In addition, many variants of uncertain signi?cance (VUSs) are found in BRCA1/2 gene testing. These VUSs mainly include missense mutations and intron muataions. However the intron muataions of BRCA1/2 are seldom studied, which is a challenge in this field. In our prior work, we screend germline mutations in BRCA1 and BRCA2 genes in 409 familial breast cancer patients in Chinese women. We found 20 Chinese-specific intron mutations of BRCA1/2. In this study, we will investigate the effect of these Chinese-specific intron mutations on the function of BRCA1/2 and evaluate the association of these mutations with breast cancer in women with these mutations in combination with clinic characteristics. We hope to reasonably explain the role of these intron mutation of BRCA1/2 in the development of breast cancer and deepen our insight into the function of BRCA1/2. In addition, the results may further guide clinical treatment of mutation carriers.