These authors contributed equally to this work.
The effect of one additional driver mutation on tumor progression
Article first published online: 10 DEC 2012
© 2012 The Authors. Evolutionary Applications published by Blackwell Publishing Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Special Issue: Evolution and Cancer
Volume 6, Issue 1, pages 34–45, January 2013
How to Cite
Reiter, J. G., Bozic, I., Allen, B., Chatterjee, K. and Nowak, M. A. (2013), The effect of one additional driver mutation on tumor progression. Evolutionary Applications, 6: 34–45. doi: 10.1111/eva.12020
- Issue published online: 21 JAN 2013
- Article first published online: 10 DEC 2012
- Manuscript Accepted: 6 SEP 2012
- Manuscript Received: 15 JUN 2012
- branching process;
- clonal expansion;
- density dependence;
- driver mutation;
- stochastic models
Tumor growth is caused by the acquisition of driver mutations, which enhance the net reproductive rate of cells. Driver mutations may increase cell division, reduce cell death, or allow cells to overcome density-limiting effects. We study the dynamics of tumor growth as one additional driver mutation is acquired. Our models are based on two-type branching processes that terminate in either tumor disappearance or tumor detection. In our first model, both cell types grow exponentially, with a faster rate for cells carrying the additional driver. We find that the additional driver mutation does not affect the survival probability of the lesion, but can substantially reduce the time to reach the detectable size if the lesion is slow growing. In our second model, cells lacking the additional driver cannot exceed a fixed carrying capacity, due to density limitations. In this case, the time to detection depends strongly on this carrying capacity. Our model provides a quantitative framework for studying tumor dynamics during different stages of progression. We observe that early, small lesions need additional drivers, while late stage metastases are only marginally affected by them. These results help to explain why additional driver mutations are typically not detected in fast-growing metastases.