Patterns of cell division and the risk of cancer

Steven A. Frank, Yoh Iwasa, Martin A. Nowak

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Epidermal and intestinal tissues divide throughout life to replace lost surface cells. These renewing tissues have long-lived basal stem cell lineages that divide many times, each division producing one stem cell and one transit cell. The transit cell divides a limited number of times, producing cells that move up from the basal layer and eventually slough off from the surface. If mutation rates are the same in stem and transit divisions, we show that minimal cancer risk is obtained by using the fewest possible stem divisions subject to the constraints imposed by the need to renew the tissue. In this case, stem cells are a necessary risk imposed by the constraints of tissue architecture. Cairns suggested that stem cells may have lower mutation rates than transit cells do. We develop a mathematical model to study the consequences of different stem and transit mutation rates. Our model shows that stem cell mutation rates two or three orders of magnitude less than transit mutation rates may favor relatively more stem divisions and fewer transit divisions, perhaps explaining how renewing tissues allocate cell divisions between long stem and short transit lineages.

Original languageEnglish
Pages (from-to)1527-1532
Number of pages6
JournalGenetics
Volume163
Issue number4
Publication statusPublished - Apr 1 2003

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Mutation Rate
Cell Division
Stem Cells
Neoplasms
Cell Lineage
Theoretical Models

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Frank, S. A., Iwasa, Y., & Nowak, M. A. (2003). Patterns of cell division and the risk of cancer. Genetics, 163(4), 1527-1532.

Patterns of cell division and the risk of cancer. / Frank, Steven A.; Iwasa, Yoh; Nowak, Martin A.

In: Genetics, Vol. 163, No. 4, 01.04.2003, p. 1527-1532.

Research output: Contribution to journalArticle

Frank, SA, Iwasa, Y & Nowak, MA 2003, 'Patterns of cell division and the risk of cancer', Genetics, vol. 163, no. 4, pp. 1527-1532.
Frank SA, Iwasa Y, Nowak MA. Patterns of cell division and the risk of cancer. Genetics. 2003 Apr 1;163(4):1527-1532.
Frank, Steven A. ; Iwasa, Yoh ; Nowak, Martin A. / Patterns of cell division and the risk of cancer. In: Genetics. 2003 ; Vol. 163, No. 4. pp. 1527-1532.
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