Tuesday, January 31, 2017

Allele Frequency Spectrum in a Cancer Cell Population

Allele Frequency Spectrum in a Cancer Cell Population

Hisashi Ohtsuki, Hideki Innan
 

Abstract

A cancer grows from a single cell, thereby constituting a large cell population. In this work, we are interested in how mutations accumulate in a cancer cell population. We provide a theoretical framework of the stochastic process in a cancer cell population and obtain near exact expressions of allele frequency spectrum or AFS (only continuous approximation is involved) from both forward and backward treatments under a simple setting; all cells undergo cell division and die at constant rates, b and d, respectively, such that the entire population grows exponentially. This setting means that once a parental cancer cell is established, in the following growth phase, all mutations are assumed to have no effect on b or d (i.e., neutral or passengers). Our theoretical results show that the difference from organismal population genetics is mainly in the coalescent time scale, and the mutation rate is defined per cell division, not per time unit (e.g., generation). Except for these two factors, the basic logic are very similar between organismal and cancer population genetics, indicating that a number of well established theories of organismal population genetics could be translated to cancer population genetics with simple modifications.