Accumulation of Driver and Passenger Mutations During Tumor Progression

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Accumulation of Driver and Passenger Mutations During Tumor Progression

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dc.contributor.author Antal, Tibor
dc.contributor.author Ohtsuki, Hisashi
dc.contributor.author Carter, Hannah
dc.contributor.author Kim, Dewey
dc.contributor.author Chen, Sining
dc.contributor.author Karchin, Rachel
dc.contributor.author Kinzler, Kenneth
dc.contributor.author Vogelstein, Bert
dc.contributor.author Bozic, Ivana
dc.contributor.author Nowak, Martin A.
dc.date.accessioned 2011-11-22T21:24:10Z
dc.date.issued 2010
dc.identifier.citation Bozic, Ivana, Tibor Antal, Hisashi Ohtsuki, Hannah Carter, Dewey Kim, Sining Chen, Rachel Karchin, Kenneth W. Kinzler, Bert Vogelstein, and Martin A. Nowak. 2010. Accumulation of driver and passenger mutations during tumor progression. Proceedings of the National Academy of Sciences 107(43): 18545. en_US
dc.identifier.issn 1091-6490 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5351640
dc.description.abstract Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a novel mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development - providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate, for the first time, the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small, 0.005 +- 0.0005, and has major implications for experimental cancer research. en_US
dc.description.sponsorship Mathematics en_US
dc.language.iso en_US en_US
dc.publisher National Academy of Sciences en_US
dc.relation.isversionof doi://10.1073/pnas.1010978107 en_US
dash.license LAA
dc.title Accumulation of Driver and Passenger Mutations During Tumor Progression en_US
dc.type Journal Article en_US
dc.description.version Author's Original en_US
dc.relation.journal Proceedings of the National Academy of Sciences en_US
dash.depositing.author Nowak, Martin A.
dash.waiver 2010-09-01
dc.date.available 2011-11-22T21:24:10Z

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  • FAS Scholarly Articles [6948]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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