Accumulation of Driver and Passenger Mutations During Tumor Progression

Accumulation of Driver and Passenger Mutations During Tumor Progression

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Accumulation of Driver and Passenger Mutations During Tumor Progression

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