Evolutionary dynamics of tumor suppressor gene inactivation
View/ Open
Author
Nowak, Martin A.
Michor, Franziska
Komarova, Natalia L.
Iwasa, Yoh
Published Version
https://doi.org/10.1073/pnas.0400747101Metadata
Show full item recordCitation
Nowak, M. A., F. Michor, N. L. Komarova, and Y. Iwasa. 2004. “Evolutionary Dynamics of Tumor Suppressor Gene Inactivation.” Proceedings of the National Academy of Sciences 101 (29): 10635–38. https://doi.org/10.1073/pnas.0400747101.Abstract
Tumor suppressor genes (TSGs) are important gatekeepers that protect against somatic evolution of cancer. Losing both alleles of a TSG in a single cell represents a step toward cancer. We study how the kinetics of TSG inactivation depends on the population size of cells and the mutation rates for the first and second hit. We calculate the probability as function of time that at least one cell has been generated with two inactivated alleles of a TSG. We find three different kinetic laws: in small, intermediate, and large populations, it takes, respectively, two, one, and zero rate-limiting steps to inactivate a TSG. We also study the effect of chromosomal and other genetic instabilities. Small lesions without genetic instability can take a very long time to inactivate the next TSG, whereas the same lesions with genetic instability pose a much greater risk for cancer progression.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#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41426806
Collections
- SPH Scholarly Articles [6329]
Contact administrator regarding this item (to report mistakes or request changes)