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Intratumor heterogeneity in evolutionary models of tumor progression.

Publication ,  Journal Article
Durrett, R; Foo, J; Leder, K; Mayberry, J; Michor, F
Published in: Genetics
June 2011

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.

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Published In

Genetics

DOI

EISSN

1943-2631

ISSN

0016-6731

Publication Date

June 2011

Volume

188

Issue

2

Start / End Page

461 / 477

Related Subject Headings

  • Tumor Microenvironment
  • Neoplasms
  • Models, Genetic
  • Humans
  • Genetic Heterogeneity
  • Disease Progression
  • Developmental Biology
  • Clone Cells
  • Cell Lineage
  • Algorithms
 

Citation

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MLA
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Durrett, R., Foo, J., Leder, K., Mayberry, J., & Michor, F. (2011). Intratumor heterogeneity in evolutionary models of tumor progression. Genetics, 188(2), 461–477. https://doi.org/10.1534/genetics.110.125724
Durrett, Rick, Jasmine Foo, Kevin Leder, John Mayberry, and Franziska Michor. “Intratumor heterogeneity in evolutionary models of tumor progression.Genetics 188, no. 2 (June 2011): 461–77. https://doi.org/10.1534/genetics.110.125724.
Durrett R, Foo J, Leder K, Mayberry J, Michor F. Intratumor heterogeneity in evolutionary models of tumor progression. Genetics. 2011 Jun;188(2):461–77.
Durrett, Rick, et al. “Intratumor heterogeneity in evolutionary models of tumor progression.Genetics, vol. 188, no. 2, June 2011, pp. 461–77. Epmc, doi:10.1534/genetics.110.125724.
Durrett R, Foo J, Leder K, Mayberry J, Michor F. Intratumor heterogeneity in evolutionary models of tumor progression. Genetics. 2011 Jun;188(2):461–477.

Published In

Genetics

DOI

EISSN

1943-2631

ISSN

0016-6731

Publication Date

June 2011

Volume

188

Issue

2

Start / End Page

461 / 477

Related Subject Headings

  • Tumor Microenvironment
  • Neoplasms
  • Models, Genetic
  • Humans
  • Genetic Heterogeneity
  • Disease Progression
  • Developmental Biology
  • Clone Cells
  • Cell Lineage
  • Algorithms