Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10635-8. Epub 2004 Jul 13.

Evolutionary dynamics of tumor suppressor gene inactivation.

Author information

  • 1Program for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138, USA. martin_novak@harvard.edu

Abstract

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.

PMID:
15252197
[PubMed - indexed for MEDLINE]
PMCID:
PMC489986
Free PMC Article

Images from this publication.See all images (2)Free text

Fig. 1.
Fig. 2.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk