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目的:研究家族性和早发性乳腺癌BRCA1基因突变情况。方法:选取52例来自不同家系家族性和早发性乳腺癌患者,提取外周血基因组DNA,对BRCA1基因的全部编码序列及外显子与内含子的拼接区进行PCR基因扩增,扩增产物经变性高效液相色谱分析(DHPLC)除筛后,对发现异常的片断进行DNA直接测序证实。结果:在52例家族性和早发性乳腺癌患者中发现4例(7.7%)BRCA1致病性突变(2257C>G,2229delAA,3413delT),其中BRCA1的2229delAA在两个不同的家系重复出现。3413delT突变未在Breast Cancer Information Core(BIC)数据库和相关的文献报道过。家族性乳腺癌突变率为12%(3/25);单纯早发性乳腺癌突变率为3.7%(1/27)。结论:BRCA1突变在山东东部地区家族性乳腺癌的发病中发挥重要作用,对具有家族史的乳腺癌家系进行BRCA1基因突变筛查具有重要意义。
Objective: To investigate the mutation of BRCA1 gene in familial and early-onset breast cancer. Methods: Totally 52 cases of patients with familial and early-onset breast cancer were enrolled in this study. Peripheral blood genomic DNA was extracted to amplify the entire coding sequence of BRCA1 gene and the splicing region of exon and intron. After the product was denuded by denaturing high performance liquid chromatography (DHPLC), the abnormal fragments were confirmed by DNA direct sequencing. RESULTS: Four (7.7%) BRCA1 causative mutations (2257C> G, 2229delAA, 3413delT) were found in 52 patients with familial and early-onset breast cancer, in which 2229delAA of BRCA1 was repeated in two different pedigrees. The 3413delT mutation was not reported in the Breast Cancer Information Core (BIC) database and related literature. The mutation rate of familial breast cancer was 12% (3/25). The mutation rate of simple early breast cancer was 3.7% (1/27). Conclusion: The BRCA1 mutation plays an important role in the pathogenesis of familial breast cancer in the eastern Shandong Province. It is of great significance to screen the BRCA1 gene mutation in pedigrees with a family history.