Evolutionary dynamics of tumor suppressor gene inactivation

Martin A. Nowak, Franziska Michor, Natalia L. Komarova, Yoh Iwasa

研究成果: Contribution to journalArticle査読

79 被引用数 (Scopus)

抄録

Tumor suppressor genes (TSGs) are important gatekeepers that protect against somatic evolution of cancer. Losing both alleles of a TSG in a single cell represents a step toward cancer. We study how the kinetics of TSG inactivation depends on the population size of cells and the mutation rates for the first and second hit. We calculate the probability as function of time that at least one cell has been generated with two inactivated alleles of a TSG. We find three different kinetic laws: in small, intermediate, and large populations, it takes, respectively, two, one, and zero rate-limiting steps to inactivate a TSG. We also study the effect of chromosomal and other genetic instabilities. Small lesions without genetic instability can take a very long time to inactivate the next TSG, whereas the same lesions with genetic instability pose a much greater risk for cancer progression.

本文言語英語
ページ(範囲)10635-10638
ページ数4
ジャーナルProceedings of the National Academy of Sciences of the United States of America
101
29
DOI
出版ステータス出版済み - 7 20 2004

All Science Journal Classification (ASJC) codes

  • 一般

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