肿瘤表观遗传学精讲.ppt

Epigenetics in cancer 肿 瘤 全球 (2010年) 809 万人死亡 1303 万新发病例 5 肝癌 1 肺癌 7 食道癌 3 结肠癌 2 乳腺癌 4 胃癌 6 宫颈癌 Cancer Cancer 6 宫颈癌 5 结肠癌 8 鼻咽癌 1 肺癌 2 肝癌 7 乳腺癌 3 胃癌 4 食道癌 268 万新发病例 197 万人死亡 中国（2010） What causes cancer? Carcinogenesis. Some factors to consider… Heredity Immunity Chemical Physical Viral Bacterial Lifestyle Heredity Genes isolated for several classic familial cancer syndromes: RB1 (retinoblastoma) APC (familial polyposis) Human Non Polyposis Colon Cancer (HNPCC) BRCA 12 (breast cancer) p53 (many cancers) 抑癌基因p53 Colleen A. Brady and Laura D. Attardi, p53 at a glance，Journal of Cell Science, 2010, 123: 2527-2532 Exposure to carcinogens, failure of DNA repair, and progressive genetic instability lead to accumulation of mutations that drive cancer development, growth, and metastases. Subclones with new mutations may become dominant within metastases or within persistent or recurrent cancer deposits through selective pressures exerted by cytotoxic or targeted chemotherapies. Cancer Epigenetics Since the discovery of the fi rst recurrent mutations in oncogenes and tumor suppressor genes, it has been clear that cancer is, in large part, a genetic disease. Global changes in the epigenetic landscape are a hallmark of cancer. What is Epigentics ? 遗传学 genetics 基因组印迹 源自双亲的两个等位基因中一个不表达或表达很弱。 不遵循孟德尔定律 同卵双胞胎 表观遗传 Why Your DNA Isn’t Your Destiny? The new field of epigenetics is showing how?your?environment and?your choices can influence?your?genetic code — and that of?your?kids 表观遗传学(Epigenetics) 基因的DNA序列不发生改变的情况下，基因的表达水平与功能发生改变，并产生可遗传的表型 一门新兴的遗传学分支 遗传与表观遗传 表观遗传学的特点： 可遗传的，即这类改变通过有丝分裂或减数分裂，能在细胞或个体世代间遗传； 可逆性的基因表达调节，也有较少的学者描述为基因活性或功能的改变； 没有DNA序列的改变或不能用DNA序列变化来解释。 拉马克 1809年发表的《动物哲学》：用进废退这种后天获得的性状是可以遗传的 表观遗传学变化具有可遗传性 Natt D, Rubin CJ, Wright D et al. Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens. BMC genomics 2012;13:59. Conclusions Our results show that epigenetic variation is inherited in chickens,