散发性乳腺癌患者BRCA1基因突变分析

Mutation analysis of BRCA1 gene in sporadic breast cancer

目的 :探讨BRCA1基因突变在散发性乳腺癌发生和发展中的作用及在乳腺癌临床诊断和治疗中的应用前景。方法 :应用PCR SSCP和直接测序法检测 3 0例散发性乳腺癌和 15例正常乳腺组织中BR CA1基因外显子 2、11和 2 0的突变情况。结果 :15例正常乳腺组织在 3个外显子上都未显示电泳异常 ,3 0例乳腺癌中有 6例在外显子 2上显示电泳条带异常 ,其中 4例经测序证实有突变 ,1例在外显子 2上 ,3例在内含子拼接区。BRCA1基因突变率在初诊年龄、临床分期和肿瘤体积上差异无统计学意义 ,但与肿瘤转移密切相关。结论 :BRCA1基因突变与散发性乳腺癌的发生和发展密切相关 ,该基因突变筛查可作为一种预后指标。

OBJECTIVE:To explore the role and types of BRCA1 gene mutation in sporadic breast cancer patients.METHODS:The mutations of exon 11,2,20 were screened by the polymerase chain reaction (PCR) and single strand conformational polymorphism (SSCP) analysis.Cases showing abnormal band-shift in SSCP were subsequently confirmed by the direct sequencing.RESULTS:Mutations were not found in all the 15 normal breast tissues.Four (13.3%) mutations were detected in 30 breast carcinomas,one of which was on exon 2,the other 3 were in intron splicing region.The relationship between BRCA1 mutations and disease characteristics was investigated, no statistical difference was found in ages at diagnosis,tumor stages and tumor volume,while BRCA1 mutation was associated with metastasis.CONCLUSION:The mutations of BRCA1 gene are involved in carcinogenesis and development of sporadic breast cancer, and the analysis of BRCA1 mutation may be useful in screening for patients with BRCA1-linked breast cancer.