RT Journal Article
SR Electronic
T1 An exactly solvable, spatial model of mutation accumulation in cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 084038
DO 10.1101/084038
A1 Chay Paterson
A1 Martin A. Nowak
A1 Bartlomiej Waclaw
YR 2016
UL http://biorxiv.org/content/early/2016/10/27/084038.abstract
AB 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.