Stochastic Tunneling of Two Mutations in a Population of Cancer Cells

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Stochastic Tunneling of Two Mutations in a Population of Cancer Cells

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

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Citation: Haeno, Hiroshi, Yosef E. Maruvka, Yoh Iwasa, and Franziska Michor. 2013. “Stochastic Tunneling of Two Mutations in a Population of Cancer Cells.” PLoS ONE 8 (6): e65724. doi:10.1371/journal.pone.0065724. http://dx.doi.org/10.1371/journal.pone.0065724.
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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.
Published Version: doi:10.1371/journal.pone.0065724
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694076/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717543
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