Somatic mutations of tumor

By | January 4, 2012

Somatic mutations in tumor DNA base sequence mainly refers to the change. The classic hypothesis that the gene mutation gene mutation 3 to 7 can cause cancer cells, somatic mutations in tumor suppressor gene mutations in activation and inactivation leads to cell cycle control is the main reason for abnormal proliferation of cancer cells.
The main basis for gene mutation hypothesis are: the DNA sequence of viral oncogenes and cellular oncogenes of DNA sequence homology; chemical carcinogenesis of the mutant gene to produce transformed cells; cell transformation in vitro experiments show that 3 to 4 genes can cause human cells to transformation; transgenic and knockout animals increased cancer rate; cancer gene mutations block the tumor cells lose the signal for tumor phenotype or apoptosis; important genetic mutations in cancer patients rate increases; many carcinogens are mutagens from most cancer gene mutation hypothesis of monoclonal tumors and cancer of the interpretation of the phenomenon: the tumor is under the action of natural selection result of the accumulation of mutations; abnormal tumor The reason is the proliferation of oncogene activation and tumor suppressor gene inactivation leads to cell cycle control results; cancerous mutations in multiple genes required for the accumulation of a very long time, Yang; accumulation of gene mutations lead to tumor evolving; tumor cells the heterogeneity of phenotype, karyotype aneuploidy and genomic instability is the result of genetic mutation, cancer requires multiple genetic mutations to complete independence, the process determines the cancer is a small probability event.
Somatic gene mutation hypothesis of cancer the following problem: from the relevant point of view, there has not been found the gene mutation, mutation rates and cancer rates is difficult to reconcile the relationship between: If you need 3 to 7 cancer gene mutation From a statistical probability of cancer is much less than the actual rate of cancer incidence, in order to explain the problem, B. vogelstein make cancer cells such as genomic instability occurs first, followed by genomic instability of a gene mutation; LA Loeb and put forward a mutant form of tumor type (mutator phenotype) the concept that tumor cells in the presence of thousands of mutations fierce, the current debate over this issue is still; mutation hypothesis suggests that the activation of oncogenes and tumor suppressor gene inactivation leads to cell cycle abnormalities leading to tumor development, draw inferences based on the hypothesis: the root cause of cancerous tumors in the cell cycle faster than normal cells, the cell cycle. But many studies have shown that tumor cells do not shorten or extend the cell cycle, tumor cell cycle is not a simple problem., cancer gene mutation hypothesis suggests that the process is to select the cells was amplified by the process of mutation positive advantage, in fact, the existence of tumor cells considerable heterogeneity, play a decisive role in tumor proliferation and only a small number of cancer stem cells, not all tumor cells, that gene mutation is not able to give all of the tumor cell phenotype of the same genetic mutation and survival advantage nature is not reversible and cumulative, so the phenotype of tumor cells should be irreversible and cumulative, but the fact is always in the tumor phenotype changes, the independent evolution of a variety of phenotypes can be reversed even; cancer cell fusion with normal total loss of cancer cell phenotype, the results support the existence of tumor suppressor genes and not due; gene mutation hypothesis of cancer-causing factors that lead to cancer through genetic mutation occurred, but now that does not cause many chemical substances mutation can induce tumor was; mutation is instantaneous events in the cell under the action of mutagenic factors gene mutation will happen soon, so cell transformation and cancer gene mutation should occur almost simultaneously, but in the carcinogenic factor in the role of cells after a few years or decades before malignant transformation; somatic gene mutations according to the tumor hypothesis that tumor cells should be diploid (diploidy) cells and normal cells differ only because of its genome some oncogenes activation and / or other tumor suppressor genes are inactivated, but in fact apart from a few transformed by a retrovirus diploid cell there, almost all of the solid tumor cells are aneuploid karyotype white; with increase with age increases the probability of tumor 1000 times, gene mutation hypothesis suggests that this is due to the accumulation of cells, the result of genetic variation, due to genetic mutation can be inherited, so young should have a higher incidence of cancer did the elderly may in fact the highest rate of occurrence of human cancer; in vitro transformation of the promoter used in the experiments are virus promoter, regulation of gene expression are much higher than the expression level of cells themselves, so the difference in gene expression experiments into the role of Yang can not be excluded; no real cancer genes, some of the classic oncogene in a different role in different tissues and cells, in some cells positive for cell proliferation, but in some cells while promoting apoptosis of aging cells.

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