Somatic evolution in cancer

Somatic evolution is the accumulation of mutations and epimutations in somatic cells (the cells of a body, as opposed to germ plasm and stem cells) during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer. Cells in pre-malignant and malignant neoplasms (tumors) evolve by natural selection. This accounts for how cancer develops from normal tissue and why it has been difficult to cure. There are three necessary and sufficient conditions for natural selection, all of which are met in a neoplasm: There must be variation in the population. Neoplasms are mosaics of different mutant cells with both genetic and epigenetic changes that distinguish them from normal cells. The variable traits must be heritable. When a cancer cell divides, both daughter cells inherit the genetic and epigenetic abnormalities of the parent cell, and may also acquire new genetic and epigenetic abnormalities in the process of cellular reproduction. That variation must affect survival or reproduction (fitness). While many of the genetic and epigenetic abnormalities in neoplasms are probably neutral evolution, many have been shown to increase the proliferation of the mutant cells, or decrease their rate of death (apoptosis). (See Hallmarks below) Cells in neoplasms compete for resources, such as oxygen and glucose, as well as space. Thus, a cell that acquires a mutation that increases its fitness will generate more daughter cells than competitor cells that lack that mutation. In this way, a population of mutant cells, called a clone, can expand in the neoplasm. Clonal expansion is the signature of natural selection in cancer. Cancer therapies act as a form of artificial selection, killing sensitive cancer cells, but leaving behind resistant cells.

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Somatic evolution in cancer

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