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,4099>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 of BRCA2 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.Genomic 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,rrAT,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.