散发性乳腺癌BRCA1基因突变及甲基化的研究-细胞生物学专业论文.docxVIP

散鬟性乳朋t癌BRCAI基因突竞及甲墓化的研究摘 散鬟性乳朋t癌BRCAI基因突竞及甲墓化的研究 摘 要 ／ ／早在70年代的流行病学研究就发现乳腺癌与遗传有关。1990年， l Hall等发现了乳腺癌及卵巢癌易感基因BRCAl，并于1994年被Miki 等成功克隆。BRCAl是一种抑癌基因，大约45％的家族性乳腺癌及 至少80％的伴发卵巢癌的早发性乳腺癌与其突变相关。V本研究采用 、 PCR．SSCP结合DNA直接测序法研究了34例散发性乳腺癌BRCA 1 基因185delAG及5382insC两个突变热点和第1 1外显子部分区域的 突变特性，结果在被检测的34例散发性乳腺癌患者中发现2例突变， 且都是在第l l外显子的2430位点发生了碱基置换，由A变成G。 提示在Ashkenazi Jewish犹太妇女中发现的两个突变热点185delAG 和5382insC不是中国乳腺癌患者的突变热点，在中国人群中进行上 述突变热点的筛查意义不大：中国散发性乳腺癌中BRCAI突变率较 低(6％)，可能与小部分散发性乳腺癌的发生相关，在普通人群中进 行广泛的BRCAl突变筛查意义不大。本研究同时采用MSREs．PCR 方法研究了34例散发性乳腺癌BRCAl基因启动子部分区域的甲基 化特点，结果发现有6例出现异常甲基化现象，其发生率较高(20％)。 筛查BRCAl基因的异常甲基化对于乳腺癌患病风险评估、早期诊断 及治疗具有重要的临床意义。 关键词BRcAl老癌；乳腺赢；甲甄；PcR-s毒薛；M§l《Es．PcR 中图法分类号 R23工9脚；2 一 ／ Il 苎兰竺塾竺竺!!坠!苎苎墨兰苎!兰!兰竺!兰 苎兰竺塾竺竺!!坠!苎苎墨兰苎!兰!兰竺!兰 一竺一 Study on BRCAl mutation and methylation in sporadic breast cancer Abstract It is showed that breast cancer is related to genetic factors by the study on epidemiology in 1970’s．Hall found breast and ovarian cancer susceptibility gene BRCAl in 1990，and in 1994 it was coloned by Miki． 、 BRCAl gene Mutation is thought to account for approximately 45％of families with significantly high breast cancer incidence，and at least 80％ of families with increased incidence of both early—onset breast cancer and ovarian cancel Study 34 Chinese sporadic breast cancer cases on BRCA 1 mutation by PCR—SSCP and DNA sequencing，find 2／34 cases existing base displace(G in place of A)in site 2430 of exon I 1．It indicates 1 85delAG and 5382insC are not the high mutation spots，so to screen them is meaningless；the low frequency(6％)of BRCAl mutation is probably related to breast cancer,and screen it is also meaningless． Study by MSREs-PCR finds 6／34 cases(20％)existing abnormal methylation．Screen the abnormal meth，7lation of BRCAl has important clinical roles in estimating the danger of cancer,early diagnosis and therapy． Postgraduate：Yao Xuemei(cell biology) Directed by：Professor Gao Jinsheng Keywords：BRCAl