山东半岛地区家族性和早发性乳腺癌BRCA2基因突变研究

Analysis ofBRCA2 gene mutations among familial and/or early-onset breast cancer patients in eastern Shandongof China

目的研究山东半岛地区家族性和早发性乳腺癌中乳腺癌易感基因BRCA2的突变位点及携带情况。方法 应用PureGene DNA纯化系统提取52例家族性和早发性乳腺癌患者的外周血单核细胞DNA，对BRCA2基因的全部编码序列及内含子和外显子拼接区进行扩增，扩增产物用变性高效液相色谱进行初筛，对发现异常片段经重新扩增后进行DNA测序证实。结果在52例乳腺癌患者中发现3个（5.8％）BRCA2的致病性突变（2001delTTAT，4099C〉T，5873C〉A）。其中，家族性乳腺癌突变率达到12％（3／25），在单纯早发性乳腺癌病例中未发现致病性突变。结论在家族性乳腺癌患者中，BRCA2基因突变可能具有重要作用，在此人群中有必要进行相关的基因检测。

Objective To investigate the prevalence ofBRCA2 gene mutations among familial and/or early-onset breast cancer patients in eastern Shandong of China. Methods Fifty-two familial and/or early-onset breast cancer patients from unrelated family were analyzed. Genornic DNA was collected from the peripheral blood mononuclear cells, the coding sequences and exon-intron boundaries of BRCA2 gene were screened using denaturing high performance liquid chromatography （DHPLC）, and the abnormal fragments were confirmed with direct DNA sequencing. Results Three mutations （5.8%） in BRCA2 gene were identified. They were 2001del TrAT, 4099C 〉 T and 5873C 〉 A. To our knowledge, all of them were firstly found in Chinese population. Furthermore, all the three mutations （12%） were identified in familial breast cancer patients, and none was in the early-onset patients. Conclusion BRCA2 may play an important role in the familial breast cancer in eastern Shandong Chinese population, but not in the early-onset breast cancer. It is necessary to give genetic test to familial breast cancer patients in this population.