肿瘤防治的新挑战-肿瘤异质性, 分子分型 及个体化冶疗PPT.ppt

肿瘤防治的新挑战(肿瘤异质性, 分子分型, 及个体化冶疗) ;我国恶性肿瘤发病及死亡情况的回顾与预测;;;肿瘤防治模式;Greenman,C et al(Nature, 2007,446:153-)reported 1,000 somatic mutations found in the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancer. Most somatic mutations are likely to be ‘passengers’ that do not contribute to oncogenesis. However, there was evidence for ‘driver’ mutation contributing to the development of the cancer studied in approximately 120 genes.;Thomas,RK et al.(Nature genetics,2007,39:347-)determined 238 known oncogen mutation across 1,000 human tumor samples of 17 cancer types. Of 17 oncogens analyzed, they found 14 to be mutated at least once, and 298(30%) samples carried at least one mutation; 1). Wood,LD,et.al determined the 乳腺癌和结直肠癌 DNA sequences based on exons of 20,857 transcript from 18,191gene. (Science,2007,Nov.16,Vol.318:1108) 2). Thomas RK,et al 分析17类肿瘤 238个oncogenes 的突变(Nature genetics, 2007: 39; 153-) 3). Greenman,C;et al. 分析210个不同人的肿瘤的 518 protein kinase gene exons 的突变 ( Nature, 2007, 446:: 153-) 两个肿瘤之间突变基因重复的很少 Pathway rather than individual genes appear to govern the course of tumorigenesis. Disruption of a pathway by mutation in any one of its genetic components would presumably lead to similar changes in growth. The differences are likely to be the basis for the wide variation in tumor behavior and responsiveness to therapy ;The epigenetic progenitor model of cancerStem/progenitor cells表观遗传学(epigenetic)改变; Gatekeeper mutation; Genetic and epigenetic instabilityFeinberg,AP et al.( Nature Review Genetics,2006,7: 21-33); 我们还不清楚一个肿瘤包含有多少个基因的改变，以及相互的作用机理？ 但研究已揭示与癌变有关的基因参与的复杂性，造戌了肿瘤病人的个体反应不同，这是肿瘤分子分型和个体化冶疗的基础 ; 肿瘤异质性, 分子型, 及个体化冶疗 Systems biology ; Diffuse large B-cell(DLBCL)(the most common subtype of non-Hodgkin’s lymphoma) Germinal centre B-like DLBCL, to express genes characteristic of germinal centre B cell,