Intratumor heterogeneity in evolutionary models of tumor progression.

Published

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

  • 21406679

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