de.mpg.escidoc.pubman.appbase.FacesBean
Deutsch
 
Hilfe Wegweiser Impressum Kontakt Einloggen
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

Genetic progression and the waiting time to cancer

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons56973

Traulsen,  Arne
Department Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, Max Planck Society;
Research Group Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society;

Externe Ressourcen
Es sind keine Externen Ressourcen verfügbar
Volltexte (frei zugänglich)

Beerenwinkel_2007.pdf
(Verlagsversion), 356KB

Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Beerenwinkel, N., Antal, T., Dingli, D., Traulsen, A., Kinzler, K. W., Velculescu, V. E., et al. (2007). Genetic progression and the waiting time to cancer. PLoS Computational Biology, 3(11): e225, pp. 2239-2246. doi:10.1371/journal.pcbi.0030225.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-000F-D746-C
Zusammenfassung
Cancer results from genetic alterations that disturb the normal cooperative behavior of cells. Recent high-throughput genomic studies of cancer cells have shown that the mutational landscape of cancer is complex and that individual cancers may evolve through mutations in as many as 20 different cancer-associated genes. We use data published by Sjoblom et al. ( 2006) to develop a new mathematical model for the somatic evolution of colorectal cancers. We employ the Wright-Fisher process for exploring the basic parameters of this evolutionary process and derive an analytical approximation for the expected waiting time to the cancer phenotype. Our results highlight the relative importance of selection over both the size of the cell population at risk and the mutation rate. The model predicts that the observed genetic diversity of cancer genomes can arise under a normal mutation rate if the average selective advantage per mutation is on the order of 1%. Increased mutation rates due to genetic instability would allow even smaller selective advantages during tumorigenesis. The complexity of cancer progression can be understood as the result of multiple sequential mutations, each of which has a relatively small but positive effect on net cell growth.