乳腺癌患者BRCA1基因启动子区甲基化模式的初步研究

A Study on Methylation Patterns of BR CA1Promoter in Patients with Bre ast Cancer

目的:探讨在散发性乳腺癌患者中乳腺癌易感基因1(breastcancer1,BRCA1)启动子区13个CpG二核苷酸甲基化模式与肿瘤发生的关系。方法:用新发展的甲基化敏感单链构象分析法methylationsensitivesinglestrandconformationanalysis,MSSSCA及DNA测序技术,对66例乳腺癌患者的癌组织、癌旁组织、外周血细胞中的BR-CA1基因启动子区甲基化模式进行研究。结果:发现有3种不同的甲基化模式。其中16例(24.2%)为高度甲基化,3例(4.5%)为部分甲基化,其余为未甲基化。结论:在部分散发性乳腺癌中BRCA1基因是高度甲基化的,它可能是BRCA1基因表达下降的机制之一。

Objective：T o investigate the relationship between methylation patterns of the １３C pG dinu cleotide sites within BRCA１promoter in sporadic br east cancer and the genesis of the tum or．Methods ：Methylation patterns of BRCA１promoter were analyzed in primary tu mor tissue，tumor－adjacent normal t issue，and blood DNA of ６６spo radic br east cancer patients，using the newly developed methylation－sensitive ，single－strand conformation analysis（MS－SSCA）and DNA sequencing techniques ．Results：Three different migration patterns were observed by MS－SSCA and were con firmed as three different methylation patterns by D NA sequencing．Among th e analyzed sa mples，１６tumors（１６／６６，２４．２％）were hypermethylated， ３tumors（３／６６，４．５％）were partially methylated，and the o thers were un methylated．Conclusion：Hypermethylation of the promoter ma y be one of the mech anisms leading to t he inactivation of BRCA１gene in some sporadic breast cance rs．