Context-dependent selection as the keystone in the somatic evolution of cancer.

Scientific Reports
B Vibishan, Milind Watve

Abstract

Somatic evolution of cancer involves a series of mutations, and attendant changes, in one or more clones of cells. A "bad luck" type model assumes chance accumulation of mutations. The clonal expansion model assumes, on the other hand, that any mutation leading to partial loss of regulation of cell proliferation will give a selective advantage to the mutant. However, a number of experiments show that an intermediate pre-cancer mutant has only a conditional selective advantage. Given that tissue microenvironmental conditions differ across individuals, this selective advantage to a mutant could be widely distributed over the population. We evaluate three models, namely "bad luck", context-independent, and context-dependent selection, in a comparative framework, on their ability to predict patterns in total incidence, age-specific incidence, stem cell number-incidence relationship and other known phenomena associated with cancers. Results show that among the factors considered in the model, context dependence is necessary and sufficient to explain observed epidemiological patterns, and that cancer evolution is largely selection-limited, rather than mutation-limited. A wide range of physiological, genetic and behavioural factors in...Continue Reading

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Citations

Mar 7, 2021·International Journal of Environmental Research and Public Health·Marion PorcherieJean-Philippe Regnaux
Mar 31, 2021·ELife·Jean-Pascal CappFrédéric Thomas

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Methods Mentioned

BETA
chromosomal aberrations

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