Stochastic Tunneling of Two Mutations in a Population of Cancer Cells

Hiroshi Haeno, Yosef E. Maruvka, Yoh Iwasa, Franziska Michor

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cancer initiation, progression, and the emergence of drug resistance are driven by specific genetic and/or epigenetic alterations such as point mutations, structural alterations, DNA methylation and histone modification changes. These alterations may confer advantageous, deleterious or neutral effects to mutated cells. Previous studies showed that cells harboring two particular alterations may arise in a fixed-size population even in the absence of an intermediate state in which cells harboring only the first alteration take over the population; this phenomenon is called stochastic tunneling. Here, we investigated a stochastic Moran model in which two alterations emerge in a cell population of fixed size. We developed a novel approach to comprehensively describe the evolutionary dynamics of stochastic tunneling of two mutations. We considered the scenarios of large mutation rates and various fitness values and validated the accuracy of the mathematical predictions with exact stochastic computer simulations. Our theory is applicable to situations in which two alterations are accumulated in a fixed-size population of binary dividing cells.

Original languageEnglish
Article numbere65724
JournalPloS one
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 26 2013

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Cells
mutation
Population Density
Mutation
Stochastic models
Histones
Population
Neoplasms
cells
population size
Histone Code
Computer simulation
Pharmaceutical Preparations
drug resistance
DNA methylation
Mutation Rate
DNA Methylation
point mutation
Point Mutation
Drug Resistance

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Stochastic Tunneling of Two Mutations in a Population of Cancer Cells. / Haeno, Hiroshi; Maruvka, Yosef E.; Iwasa, Yoh; Michor, Franziska.

In: PloS one, Vol. 8, No. 6, e65724, 26.06.2013.

Research output: Contribution to journalArticle

Haeno, Hiroshi ; Maruvka, Yosef E. ; Iwasa, Yoh ; Michor, Franziska. / Stochastic Tunneling of Two Mutations in a Population of Cancer Cells. In: PloS one. 2013 ; Vol. 8, No. 6.
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