Regensburg 2016 – scientific programme

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BP: Fachverband Biologische Physik

BP 2: Physics of Cancer

BP 2.2: Talk

Monday, March 7, 2016, 10:00–10:15, H43

Stochastic tunneling and metastable states during the somatic evolution of cancer — Peter Ashcroft¹, Franziska Michor², and •Tobias Galla¹ — ¹School of Physics and Astronomy, The University of Manchester, UK — ²Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

Tumors initiate when a population of cells accumulates a certain number of genetic and/or epigenetic alterations. Sometimes an intermediate mutant in a sequence does not reach fixation before generating a double mutant, this is referred to as `stochastic tunelling'. Here, we focus on stochastic tunneling in a Moran model. Our analysis reveals fitness landscapes and mutation rates for which finite populations are found in long-lived metastable states. The escape from these states is driven by intrinsic noise, and their location affects the probability of tunneling. In these regimes it is the escape from the metastable states that is the key bottleneck; fixation is no longer limited by the emergence of a successful mutant lineage. We use the Wentzel-Kramers-Brillouin (WKB) method to compute fixation times, successfully validated by stochastic simulations. Our work fills a gap left by previous approaches and provides a more comprehensive description of the acquisition of multiple mutations in populations of somatic cells.

Reference: P. Ashcroft, F. Michor, T. Galla, Genetics 199 (2015) 1213.