Evolutionary dynamics of tumor progression with random fitness values Journal Article


Authors: Durrett, R.; Foo, J.; Leder, K.; Mayberry, J.; Michor, F.
Article Title: Evolutionary dynamics of tumor progression with random fitness values
Abstract: 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 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. © 2010 Elsevier Inc.
Keywords: genetics; mutation; disease course; united states; neoplasm; neoplasms; phenotype; cytology; biological model; statistics; evolution; models, theoretical; poisson distribution; disease progression; models, genetic; fitness; hominid; tumor; stochastic processes; polymorphism, genetic; theoretical model; genetic polymorphism; beneficial fitness effects; branching process; cancer evolution; fitness distribution; mutational landscape; numerical model; reproductive fitness; statistical distribution; biological evolution; genetic fitness; statistical distributions
Journal Title: Theoretical Population Biology
Volume: 78
Issue: 1
ISSN: 0040-5809
Publisher: Elsevier Inc.  
Date Published: 2010-08-01
Start Page: 54
End Page: 66
Language: English
DOI: 10.1016/j.tpb.2010.05.001
PUBMED: 20488197
PROVIDER: scopus
PMCID: PMC2929987
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: TLPBA" - "Source: Scopus"
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  1. Franziska Michor
    23 Michor
  2. Kevin Leder
    1 Leder
  3. Jasmine Yen-Teng Foo
    6 Foo