Mathematics – Probability
Scientific paper
2010-03-09
Theoretical Population Biology, Volume 78, Issue 1, August 2010, Pages 54-66
Mathematics
Probability
33 pages, 2 Figures
Scientific paper
10.1016/j.tpb.2010.05.001
Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis. Other mutations, however, do not change the phenotype of the cell or even decrease cellular fitness. While much experimental effort is being devoted to the identification of the different functional effects of individual mutations, mathematical modeling of tumor progression generally considers constant fitness increments as mutations are accumulated. In this paper we study a mathematical model of tumor progression with random fitness increments. We analyze a multi-type branching process in which cells accumulate mutations whose fitness effects are chosen from a distribution. We determine the effect of the fitness distribution on the growth kinetics of the tumor. This work contributes to a quantitative understanding of the accumulation of mutations leading to cancer phenotypes.
Durrett Rick
Foo Jasmine
Leder Kevin
Mayberry John
Michor Franziska
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