Spatial structure increases the waiting time for cancer: Paper

Publication: Research - peer-reviewJournal article – Annual report year: 2011

Without internal affiliation

  • Author: Martens, Erik A

    Unknown

  • Author: Kostadinov, Rumen

    School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

  • Author: Maley, Carlo C

    Center for Evolution and Cancer, Helen Diller Family Comprehensive Cancer Center, and Department of Surgery, University of California, San Francisco, CA, USA

  • Author: Hallatschek, Oskar

    Max Planck Research Group for Biophysics and Evolutionary Dynamics, MPI for Dynamics and Self-Organization, Göttingen, Germany

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Cancer results from a sequence of genetic and epigenetic changes that lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells and thus to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been attracting increasing interest in recent years. A great deal of effort has been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to assess two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones and decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale Lc. These characteristic features of clonal interference may help us to predict the onset of cancers with pronounced spatial structure and to interpret spatially sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progression of colon cancer and possibly other cancers where spatial structure matters.
Original languageEnglish
JournalNew Journal of Physics
Publication date2011
Volume13
Issue11
ISSN1367-2630
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 14
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