乳腺癌BRCA1基因突变的研究

目的　乳腺癌易感基因 (BRCA1基因 )是一种抑癌基因。本研究检测BRCA1基因在乳腺癌中的突变情况 ,探讨BRCA1基因突变与乳腺癌的关系。方法　选取 89例乳腺癌患者标本作实验组 ,另取非癌乳腺组织标本 30例作对照组。每一例标本分别捣碎 ,分别用酚 -氯仿抽提法提取DNA ,每例DNA用PCR扩增BRCA1基因的 2、5、1 7、2 0等 4个外显子。分别将每例病人每个外显子的PCR扩增产物进行SSCP分析 ,对出现异常区带的PCR扩增产物进行DNA测序 ,与基因库序列比对分析其突变情况。结果　 30例非癌乳腺组织未检测出BRCA1基因突变 ,89例乳腺癌共检测出 4例突变 ,其中 2例为 5外显子的错义突变 (2 73C >G ,2 87A >T) ,2例为 1 7外显子的错义突变 (5 1 1 5T >C ,5 1 1 6A >G)。乳腺癌BRCA1的基因突变率为 4 5 %(4 / 89)。结论　BRCA1突变与乳腺癌有关系 ,检测BRCA1基因突变对于乳腺癌患病风险评估及早期诊断具有重要意义

BRCA1 gene mutations in human breast Cancer

Objective Breast cancer susceptibility gene(BRCA1 gene) is known as a kind of anti oncogene.This study was to assay BRCA1 gene mutation in breast cancer,and to study the relationship between BRCA1 mutation and breast cancer.Methods Breast cancer tissues of 89 patients were studied,and breast tissues of 30 cases of patients without cancer were randomly selected as controls.Each tissue sample was ground thoroughly in mortar with pestle.DNA was extracted by the phenol chloroform method.Fragments of exon 2,5,17 and 20 of BRCA1 gene were amplified by PCR.Mutational screening was performed by single strand conformation polymorphism analysis(SSCP),and alterations were confirmed by DNA sequencing.Results A total of 4 single nucleotide changes in BRCA1 were identified,including 2 missense mutations in exon 5(273C>G,287A>T),2 missense mutations in exon 17(5115T>C,5116A>G).the mutation rate was 4 5%(4/89).No mutation was identified in the controls.Conclusions Mutations in BRCA1 is related to breast cancer,and BRCA1 mutation may play an important role in the risk value and early diagnosis.