09肿瘤遗传学案例介绍.ppt

第十七章 肿瘤 肿瘤的遗传学 肿瘤的多步骤发生 肿瘤的遗传学改变 所有的癌症都是遗传性疾病-因为癌症是由体细胞的一系列的基因突变引起的。 大约有 10% 癌症病人带有先天性的遗传缺陷，这个遗传缺陷使得他们整个一生中患癌症的机会大幅度上升。 三类基因的突变导致癌症的发生：1. 癌基因（Oncogene），一般情况下促进细胞生长。(ras, EGF, Neu) 2. 抑癌基因（Tumor Suppressor Genes ），抑制细胞生长，促进细胞分化或凋亡（APC,BRCA1, BRCA2）。这两类基因的协同作用下，细胞就可以癌变。3. 细胞维稳基因。修复DNA损伤，避免基因突变(Rad 51, ATM)。 多次突变学说。The multi-mutation theory on cancer was proposed by Nordling in the British Journal of Cancer in 1953. Knudson，multiple “hits” to DNA were necessary to cause cancer. In the children with inherited retinoblastoma, the first insult was inherited in the DNA, and any second insult would rapidly lead to cancer. In non-inherited retinoblastoma, two “hits” had to take place before a tumor could develop, explaining the age difference. Rb, APC 癌症是免疫性疾病吗？ Immunity and Cancer Immunoediting：Immunoediting is a process by which a person is protected from cancer growth and the development of tumour immunogenicity by their immune system. 1. Elimination phase 2. Equilibrium 3. Escape Chronic inflammation, on theother hand, has been shownto contribute to tumorigenesisat all stages. It contributes tocancer initiation by generatinggenotoxic stress, to cancer promotion by inducing cellular proliferation, and to cancer progression byenhancing angiogenesis and tissue invasion. 主要细胞激活信号传递途径 肿瘤抑制基因p53 信号传递途径 细胞的主要信号传递途径(Major signalling pathways in cell) 第一节 肿瘤发生的遗传学基础 一、单基因遗传的肿瘤：视网膜母细胞瘤 (Rb); 乳腺癌(BRCA1，BRCA2); 结肠癌(APC) 二、多基因遗传的肿瘤：胃癌、肺癌、前列腺癌、子宫颈癌。芳羟化酶（arylhydrocarbon hydroxylase，AHH；OMIM#108340） 三、染色体畸变：The exact chromosomal defect in Philadelphia chromosome is a translocation. Parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 (region q34) to a part of the BCR (breakpoint cluster region) gene on chromosome 22 (region q11). This is a reciprocal translocation, creating an elongated chromosome 9 (der 9), and an truncated chromosome 22 (the Philadelphia chromosome).BCR-A