Intratumor heterogeneity in evolutionary models of tumor progression

Rick Durrett, Jasmine Foo, Kevin Leder, John Mayberry, Franziska Michor

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)461-477
Number of pages17
JournalGenetics
Volume188
Issue number2
DOIs
StatePublished - Jun 1 2011

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