甲基化与乳腺癌

According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
去甲基化
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
DNA甲基化是靠DNMT来维持，目前去甲基化药物主要指DNMT抑制剂， 它通过抑制DNMT来恢复抑癌基因的功能，从而达到治疗肿瘤的目的。 DNMT抑制剂治疗肿瘤的作用机理：
正常组织在某些因素的作
去甲基化药物通过抑
用下转化为恶性肿瘤时，抑
制DNMT的活性使复制后的
癌基因也经历着从正常表达、 DNA不能再次甲基化，这就
DNA去甲基化治疗药物
1.核苷类DNMT抑制剂，如5-氮胞苷及其脱氧核糖类 （具有很强的甲基化抑制作用，第一个被美国FDA批准 上市治疗恶性肿瘤的去甲基化药物，主要用于骨髓增生 异常综合征，还可用于白血病）； 2.非核苷类弱DNMT抑制剂，如肼屈嗪，普鲁卡因等 （较弱的去甲基化作用，限制了其临床应用）； 3.自行设计的抑制剂，如RG108（直接并特异性地作用 于DNMT）
DNA去甲基化的药物治疗对血液学方面的肿瘤疗效好，而对 实体肿瘤则不像预期的那样有效，可能的原因是药理学及药
代学方面的机制不同，其他原因：
DNMT有3种，它们之间 存在协同作用，需同时
抑制几种DNMT才能为 临床治疗带来最佳疗效
发挥作用的前提是 细胞DNA合成处于旺盛期，
对于增殖低下的细胞如肿 瘤干细胞不敏感
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
DNA甲基化和组蛋白乙酰化酶抑制剂联合使 用，如5-氮胞苷和丁酸苯酯、地西他滨和 丙戊酸联合用药。
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
表观遗传学
表观遗传学( epigenetics)是指无序列改变的 DNA 或染色体因修饰作用引起的基因表达 改变, 它发生在DNA 复制后的转录或 mRNA 的翻译过程, 并且能在细胞增殖过程 中稳定传递。表观遗传主要涉及DNA 甲基
化、染色质重塑、基因组印记和非编码 RNA 的基因表达调控等。
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
乳 腺 癌 超 甲 基 化 相 关 基 因
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
DNA甲基化
超甲基化
低甲基化
去甲基化
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
DNA甲基化检测方法
传统的整体水平甲基化分析 方法：如高效液相色谱柱 及相关方法、SssI甲基转 移酶法、免疫化学法、氯 乙醛法；
特异性位点的DNA甲基化检 测：如甲基化敏感性限制 性内切酶、直接测序法等。
Fra Baidu bibliotek
定量多重甲基化特异性 PCR(QM-MSP)是一种特 异位点甲基化检测技术。 其基本原理是用亚硫酸氢 钠处理基因组DNA,未甲基 化的胞嘧啶变成尿嘧啶,而 甲基化的胞嘧啶不变。因 此从理论上讲,用不同的引 物PCR,即可检测出这种差 异,从而确定基因是否有 CpG岛。
超甲基化
发生在DNA 启动子区CpG 岛的超甲基化是 最主要的表观遗传学改变,DNA 超甲基化使 抑癌基因表达沉寂, 失去抑制细胞异常增殖 和转移的功能,多种抑癌基因启动子区的超 甲基化与乳腺癌的进展和转移相关。
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
D
DNA 甲基化是表观遗传学研究最深
N
入的一种机制。DNA 甲基化是指由
A
DNA 甲基转移酶( DNMT) 催化， 将活性甲基从S-腺苷甲硫氨酸转移
甲
至胞嘧啶的C 5 位上，形成5-甲基
基
胞嘧啶的化学修饰过程，是一种表 观遗传修饰。
化
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
启动区未甲基化到基因沉默、启动 导致所有等位基因表现为去甲
区高甲基化的转变，DNMT在这 一转变过程中的作用有二，一
基化，从而使抑癌基因得以恢
是激活启动区从未甲基化到
复、重新抑制肿瘤的生长。
高甲基化，二是使之在每
一轮DNA复制以后仍保
持着高甲基化状态。
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
低甲基化
▪ 低甲基化是基因组整体甲基化水平降低, 导 致遗传不稳定性增加。原癌基因在正常组 织中因甲基化表达受抑制, 在肿瘤中呈低甲 基化而活化为癌基因。
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
人乳腺癌易感基因1( BRCA1) 上皮E-钙黏蛋白( CDH 1)
肿瘤高甲基化基因-1(H IC1 ) 结肠腺瘤性息肉病基因(APC)
雌激素受体A(ESR1) 甲状腺激素受体1 (TRB1 )
视黄醛酸B 受体(RAR-B) 细胞周期蛋白依赖型激酶抑制剂2(p16)
谷胱甘肽-S-转移酶(GSTP) 细胞周期蛋白D2( cyclin D2)
DNA 甲基化在乳腺癌早期诊断中的应用
经性原癌乳率诊研息位均腺很断究肉癌有癌低有证病和甲组，一(实不基织这定A，同化中对临PC结分发甲早床)肠期生基期意基腺的，化乳义因瘤乳而发腺。在腺在生癌非频的C乳y可c液腺可l以i期n中癌能在用诊D进组作血2于断行织为甲清临的检中乳基或床标测出腺化乳。志，现癌几头应这，早乎抽有并只吸且在
浅谈DNA甲基化与乳腺癌
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
核突触蛋白-C (SNCG)
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline
According to the assessment requirements of party conduct and clean government, combined with the "five regulations" and "five new requirements" of state-owned Enterprise leaders ' integrity and self-discipline