家族性和早发性乳腺癌BRCA1基因突变分析

目的 分析中国黑龙江省家族性和早发性乳腺癌中BRCA1基因的突变情况。方法 以黑龙江地区的92例家族性和早发性乳腺癌(发病年龄≤35岁)为研究对象。由静脉血提取基因组DNA,对BRCA1基因的全部编码序列(除外1,4号外显子)进行扩增。由聚丙烯酰胺凝胶电泳分析(SSCP)进行突变的初筛,之后进行DNA直接测序证实。结果 在92例乳腺癌患者中发现有5种致病性突变,其中3种为新发现的突变,发现的已报道的2种突变均为无义突变。结论 在中国黑龙江人群中,BRCA1基因的突变对于遗传性乳腺癌的发生可能具有较重要意义;新发现的3个突变位点可能是中国人群中的特有突变;黑龙江地区BRCA1在家族性乳腺癌中突变率明显低于国内外报道,但其中的移码突变3712insG分别在3个患者中检出,提示有可能成为该地区的基础突变。

BRCA1 gene mutations analysis of familial breast cancer and early-onset breast cancer

Objective BRCA1 has been known as breast cancer susceptibility genes which is closely associated with familial breast cancer and early onset breast cancer. The objective of our research is to investigate the prevalence of BRCA1 gene mutations among HeiLongJiang patients with familial or at early onset breast cancer. Methods 92 breast cancer patients with familial history or have suffered from breast cancer at the age of less than 35 years old were analyzed. A comprehensive mutation analysis （ except exonl and exon4 ） was performed through SSCP and subsequent DNA direct sequencing. Results In 92 breast cancers,five mutations were identi- fied that included 3 novel mutations and 2 previously reported mutations which are all nonsense mutation. Conclusion The BRCAI may play a very important role in familial breast cancer of HeiLongJiang population. Three novel mutations in BRCAI may be mutations characterized to familial breast cancer of Chinese HeiLongJiang population. The mutation frequency of BRCA1 in familial breast cancer patients from HeiLongJiang is obviously lower than that in the western countries. However,the nonsense mutation 3712insG were detected in three patients which indicated that this mutation may be a founder mutation.