Evolutionary dynamics of tumor suppressor gene inactivation
AUTOR(ES)
Nowak, Martin A.
FONTE
National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=489986Documentos Relacionados
- Mechanism for Mutational Inactivation of the Tumor Suppressor Smad2
- Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins
- Vascular tumors in livers with targeted inactivation of the von Hippel–Lindau tumor suppressor
- The optimal rate of chromosome loss for the inactivation of tumor suppressor genes in cancer
- Structure of the rat p53 tumor suppressor gene.