title: Intratumor heterogeneity in evolutionary models of tumor progression.
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.
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina 27708, USA. rtd@math.duke.edu
authors.forename: Rick
authors.initials: R
authors.lastname: Durrett
authors.forename: Jasmine
authors.initials: J
authors.lastname: Foo
authors.forename: Kevin
authors.initials: K
authors.lastname: Leder
authors.forename: John
authors.initials: J
authors.lastname: Mayberry
authors.forename: Franziska
authors.initials: F
authors.lastname: Michor
mesh_terms: D000465:Algorithms; D019070:Cell Lineage / Q000235:genetics*; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D018740:Genetic Heterogeneity; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics