Intratumor heterogeneity in evolutionary models of tumor progression.
Journal Article (Journal Article)
With rare exceptions, human tumors arise from single cells that have accumulated the necessary number and types of heritable alterations. Each such cell leads to dysregulated growth and eventually the formation of a tumor. Despite their monoclonal origin, at the time of diagnosis most tumors show a striking amount of intratumor heterogeneity in all measurable phenotypes; such heterogeneity has implications for diagnosis, treatment efficacy, and the identification of drug targets. An understanding of the extent and evolution of intratumor heterogeneity is therefore of direct clinical importance. In this article, we investigate the evolutionary dynamics of heterogeneity arising during exponential expansion of a tumor cell population, in which heritable alterations confer random fitness changes to cells. We obtain analytical estimates for the extent of heterogeneity and quantify the effects of system parameters on this tumor trait. Our work contributes to a mathematical understanding of intratumor heterogeneity and is also applicable to organisms like bacteria, agricultural pests, and other microbes.
Full Text
Duke Authors
Cited Authors
- Durrett, R; Foo, J; Leder, K; Mayberry, J; Michor, F
Published Date
- June 2011
Published In
Volume / Issue
- 188 / 2
Start / End Page
- 461 - 477
PubMed ID
- 21406679
Pubmed Central ID
- PMC3122322
Electronic International Standard Serial Number (EISSN)
- 1943-2631
International Standard Serial Number (ISSN)
- 0016-6731
Digital Object Identifier (DOI)
- 10.1534/genetics.110.125724
Language
- eng