医学遗传学课件：Chapter 16 Tumor.pptVIP

Chromosome aberration can be seen in most of tumor cell. Chromosome usually has same feature in the same tumor cells. Environmental agent can make for the adversity of karyotype in tumor cells . Oncogene theory 肿瘤发生的癌基因理论 Oncogene are molecular basis of origin and development of cancers Oncogenes are genes that are associated with the development of cancers When a POG mutates (changes) into an oncogene, it becomes permanently turned on or activated when it is not supposed to be. When this occurs, the cell divides too quickly, which can lead to cancer. POG are concerned with normal cell division, cell growth, and cell differentiates during embryogenesis. Two mutation theory (The Knudson Hypothesis) Two mutation theory was first proposed in the early 1970s by Alfred Knudson as an explanation for hereditary retinoblastoma. An elegant series of experiments beginning in the mid 1980s proved Knudsons hypothesis to be remarkably accurate. Tumor Suppressor Gene theory 肿瘤发生的肿瘤抑制基因理论 Two Mutation Theory Two mutations are required, one in each copy of the rb gene The first mutation is present in the germline and thus in all cells of the body For familial cases The second somatic mutation is necessary for initiating tumor formation Inherited cancer Initiation Promotion Sporadic cancer Initiation Knudson提出了二次突变学说 LOH (loss of heterozygosity) 细胞有丝分裂异常导致以杂合状态存在的一个与突变基因对应的正常基因丢失，从而失去对肿瘤发生的抑制作用。 Loss of a normal allele from a region of one cs of a pair, allowing a defective allele on the homologous cs to be clinically manifest. A feature of many cases of retinoblastoma, breast cancer, and other tumors due to mutation in a TSG. Loss of Heterozygosity malignant transformation RB Loss of Heterozygosity RB rb gene conversion The development of tumor is a multi-step process, and diverse related gene involved. Oncogene activation and depletion or deactivation of anti-oncogene to promote cell proliferation →cell aggrava