TY - JOUR T1 - Spatial structure governs the mode of tumour evolution JF - bioRxiv DO - 10.1101/586735 SP - 586735 AU - Robert Noble AU - Dominik Burri AU - Jakob Nikolas Kather AU - Niko Beerenwinkel Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/23/586735.abstract N2 - Characterizing the mode – the way, manner, or pattern – of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. DNA sequencing studies have inferred various modes, including branching, punctuated and neutral evolution, but it is unclear why a particular pattern predominates in any given tumour [1]. Here we propose that differences in tumour architecture alone can explain the variety of observed patterns. We examine this hypothesis using spatially explicit population genetic models and demonstrate that, within biologically relevant parameter ranges, tumours are expected to exhibit diverse evolutionary modes including four archetypal “oncoevotypes”: rapid clonal expansion (predicted in leukaemia); progressive diversification (in colorectal adenomas and early-stage colorectal carcinomas); branching evolution (in invasive glandular tumours); and almost neutral evolution (in certain non-glandular and poorly differentiated solid tumours). We thus provide a simple, mechanistic explanation for a wide range of empirical observations. Oncoevotypes are driven by differences in cell dispersal and cell-cell interactions, which we show are essential for accurately characterizing, forecasting and controlling tumour evolution. ER -