Metapopulation dynamics and spatial heterogeneity in cancer

摘要: With the advent of drugs targeting specific molecular defects in cancerous cells [Gorre, M. E., et al. (2001) Science 293, 876–880], it is important to understand degree genetic heterogeneity present tumor cell populations and rules that govern microdiversity human cancer. Here, we first show with different genotypes genes influencing growth programmed death coexist advanced malignant tumors colon, exhibiting microsatellite instability. Detailed, physical mapping diverse shows them be arranged small, intermingling areas, resulting a variegated pattern diversity. Using computational modeling experimental data, find coexistence between similar competitors enhanced, instead deterred, by spatial dynamics [Hanski, I. (1999) Metapopulation Dynamics (Oxford Univ. Press, New York)]. The model suggests simple plausible scenario for generation during progression. emergence persistence patterns diversity encountered can generated without need invoke differences mutation rates, neutrality interactions, or separated time scales. We posit apply ecology explain maintenance are also at work may underlie microheterogeneity.