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dc.contributor.authorHaeno, Hiroshien_US
dc.contributor.authorMaruvka, Yosef E.en_US
dc.contributor.authorIwasa, Yohen_US
dc.contributor.authorMichor, Franziskaen_US
dc.date.accessioned2014-02-18T18:11:03Z
dc.date.issued2013en_US
dc.identifier.citationHaeno, 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.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11717543
dc.description.abstractCancer 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.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0065724en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694076/pdf/en
dash.licenseLAAen_US
dc.subjectMathematicsen
dc.subjectApplied Mathematicsen
dc.subjectProbability Theoryen
dc.subjectMedicineen
dc.subjectOncologyen
dc.titleStochastic Tunneling of Two Mutations in a Population of Cancer Cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorMaruvka, Yosef E.en_US
dc.date.available2014-02-18T18:11:03Z
dc.identifier.doi10.1371/journal.pone.0065724*
dash.contributor.affiliatedMaruvka, Yosef
dash.contributor.affiliatedMichor, Franziska


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