肿瘤的遗传咨询培训课件.ppt

Tumor cells may enter the blood stream passively or actively via biological events such as EMT or centrosomes amplification.Disseminating tumor cells must overcome several Hurdles including anoikis,shear stress in the bloodstream,and the immune system in-and outside of the blood circulation.Once at a distant site,tumor cells may extravasate, undergo MET, and grow locally to become a metastasis or remain in dormancy.选择压力下或特定的微环境中，部分肿瘤细胞可以通过EMT获得肿瘤干细胞特性，进入血液，克服凋亡，血液的剪切压力，逃避免疫系统，并移植到远处器官和/或组织。 * Figure 1: CTCs as snapshot of the evolving tumor landscape. Clonal evolution depicted as emergence of clones after acquisition of driver mutations. New (sub) clones derive from ancestral clones following linear and branched evolution. Outgrowth and repression (therapeutic or outcompeting) of these subclones can lead to emergence and disappearance of driver mutations respectively. Seeding and re?seeding of tumor cells causes development of changing tumor landscapes at multiple sites. Selective therapy pressure can lead to outgrowth of resistant clones at time of disease progression. CTCs sampling can function as a snapshot of the overall tumor bulk (primary tumor?and?metastases).?When?profiling?CTCs?at?multiple?time?points?emerging?and?decreasing?subclones?can?be?unveiled.?Techniques?to? profile?CTCs?include?phenotypical?and?molecular?analyses. CTC作为肿瘤进化图谱的快照。 克隆进化的定义是肿瘤细胞获得driver mutations (驱动突变) 突变后出现的的克隆。新(子)克隆靠原代克隆线性和分支性进化而来。这些子克隆的新生物或者退行(治疗或其他竞争因素)的积累会导致这些驱动突变的出现和消失。肿瘤细胞的播种 和再播种导致肿瘤在不同的器官发生不同的改变。 选择性治疗压力会导致耐药克隆的新生，在疾病进展的时间。ctc抽样可以作为整个肿瘤的快照(原发肿瘤和转移)。在不同时间点对CTC检测（表型和分子特征分析），可以发现新出现或是消退的子克隆。 WGA：全基因组扩增方法于1992年开发是一种增加有限的DNA样本的数量的方法。而基于微阵列技术的比较基因组杂交（aCGH）通过在一张芯片上用标记不同荧光素的样品（肿瘤样品和对照样品）同时进行杂交可检测样本基因组和对照基因组间DNA拷贝数变化（CNV），常用于肿瘤及遗传性疾病全基因组CNV检测，直观地表现出肿瘤及遗传性疾病基因组DNA在整个染色体组的缺失或扩增，对肿瘤而言缺失部位可能包含抑癌基因，而扩增片段则可能存在致癌基因。 * * Fig. 2. Analytic tools for analysis of CTCs after isolation. 1: Immunophenotyping employs antibodies to label proteins for CTC detection and character