Normal tissue architecture determines the evolutionary course of cancer

• DOI: 10.1038/s41467-021-22123-1
• Publication Date: 2021-04-06T10:02:48Z
• Authors: Jeffrey West; Ryan O. Schenck; Chandler Gatenbee; Mark Robertson-Tessi; Alexander R. A. A...
• Keywords: Evolutionary Dynamics

Abstract Cancer growth can be described as a caricature of the renewal process tissue origin, where architecture has strong influence on evolutionary dynamics within tumor. Using classic, well-studied model tumor evolution (a passenger-driver mutation model) we systematically alter spatial constraints and cell mixing rates to show how structure influences functional (driver) mutations genetic heterogeneity over time. This approach explores key mechanism behind both inter-patient intratumoral heterogeneity: competition for space. Time-varying leads an emergent transition from Darwinian premalignant subsequent invasive neutral growth. Initial determine mode (Darwinian neutral) without change in cell-specific rate or fitness effects. Driver acquisition during precancerous stage may modulated en route by combination two factors: limited cellular mixing. These factors occur naturally ductal carcinomas, branching topology network dictates rates.