Somatic selection for and against cancer

Franziska Michor, Steven A. Frank, Robert M. May, Yoh Iwasa, Martin A. Nowak

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

In multicellular organisms, cells cooperate within a well-defined developmental program. Cancer is a breakdown of such cooperation: cells mutate to phenotypes of uncoordinated proliferation. We study basic principles of the architecture of solid tissues that influence the rate of cancer initiation. In particular, we explore how somatic selection acts to prevent or to promote cancer. Cells with mutations in oncogenes or tumor suppressor genes often have increased proliferation rates. Somatic selection increases their abundance and thus enhances the risk of cancer. Many potentially harmful mutations, however, increase the probability of triggering apoptosis and, hence, initially lead to cells with reduced net proliferation rates. Such cells are eliminated by somatic selection, which therefore also works to reduce the risk of cancer. We show that a tissue organization into small compartments avoids the rapid spread of mutations in oncogenes and tumor suppressor genes, but promotes genetic instability. In small compartments, genetic instability, which confers a selective disadvantage for the cell, can spread by random drift. If both deleterious and advantageous mutations participate in tumor initiation, then we find an intermediate optimum for the compartment size.

Original languageEnglish
Pages (from-to)377-382
Number of pages6
JournalJournal of Theoretical Biology
Volume225
Issue number3
DOIs
Publication statusPublished - Dec 7 2003

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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