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Extreme value statistics of mutation accumulation in renewing cell populations

Accepted version
Peer-reviewed

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Authors

Greulich, P 
Simons, BD 

Abstract

The emergence of a predominant phenotype within a cell population is often triggered by the chance accumulation of a sequence of rare genomic DNA mutations within a single cell. For example, tumors may be initiated by a single cell in which multiple mutations cooperate to bypass their natural defense mechanism. The risk of such an event is thus determined by the extremal accumulation of mutations across tissue cells. To address this risk, here we study the statistics of the maximum mutation numbers in a generic, but tested, model of a renewing cell population. By drawing an analogy between the genealogy of a cell population and the theory of branching random walks, we obtain analytical estimates for the probability of exceeding a threshold number of mutations to trigger a proliferative advantage of a cell over its neighbors, and determine how the statistical distribution of maximum mutation numbers scales with age and cell population size.

Description

Keywords

49 Mathematical Sciences, 4905 Statistics, Genetics, 2.1 Biological and endogenous factors, Cancer

Journal Title

Physical Review E

Conference Name

Journal ISSN

2470-0045
2470-0053

Volume Title

98

Publisher

American Physical Society (APS)
Sponsorship
Engineering and Physical Sciences Research Council (EP/P034616/1)
Medical Research Council (MC_PC_12009)
EPSRC