title: An exactly solvable, spatial model of mutation accumulation in cancer.
abstract: One of the hallmarks of cancer is the accumulation of driver mutations which increase the net reproductive rate of cancer cells and allow them to spread. This process has been studied in mathematical models of well mixed populations, and in computer simulations of three-dimensional spatial models. But the computational complexity of these more realistic, spatial models makes it difficult to simulate realistically large and clinically detectable solid tumours. Here we describe an exactly solvable mathematical model of a tumour featuring replication, mutation and local migration of cancer cells. The model predicts a quasi-exponential growth of large tumours, even if different fragments of the tumour grow sub-exponentially due to nutrient and space limitations. The model reproduces clinically observed tumour growth times using biologically plausible rates for cell birth, death, and migration rates. We also show that the expected number of accumulated driver mutations increases exponentially in time if the average fitness gain per driver is constant, and that it reaches a plateau if the gains decrease over time. We discuss the realism of the underlying assumptions and possible extensions of the model.
authors.affiliation: SUPA, School of Physics and Astronomy, The University of Edinburgh, Peter Guthrie Tait Road, Edinburgh EH9 3FD, United Kingdom.
authors.forename: Chay
authors.initials: C
authors.lastname: Paterson
authors.affiliation: Program for Evolutionary Dynamics, Harvard University, One Brattle Square, Cambridge, Massachusetts, USA.|Department of Mathematics, Harvard University, One Oxford Street, Cambridge, Massachusetts, USA.|Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge, Massachusetts, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Nowak
authors.affiliation: SUPA, School of Physics and Astronomy, The University of Edinburgh, Peter Guthrie Tait Road, Edinburgh EH9 3FD, United Kingdom.|SynthSys-Synthetic &Systems Biology, The University of Edinburgh, Edinburgh EH9 3BF, United Kingdom.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Waclaw
mesh_terms: D000465:Algorithms; D002465:Cell Movement; D003198:Computer Simulation; D005838:Genotype; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D009154:Mutation; D000067552:Mutation Accumulation; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D013269:Stochastic Processes; D013997:Time Factors