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Forward and backward evolutionary processes and allele frequency spectrum in a cancer cell population

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  • Ohtsuki, Hisashi
  • Innan, Hideki

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 divisions 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 is 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.

Suggested Citation

  • Ohtsuki, Hisashi & Innan, Hideki, 2017. "Forward and backward evolutionary processes and allele frequency spectrum in a cancer cell population," Theoretical Population Biology, Elsevier, vol. 117(C), pages 43-50.
    • Handle: RePEc:eee:thpobi:v:117:y:2017:i:c:p:43-50
    DOI: 10.1016/j.tpb.2017.08.006
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    References listed on IDEAS

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    1. Bartlomiej Waclaw & Ivana Bozic & Meredith E. Pittman & Ralph H. Hruban & Bert Vogelstein & Martin A. Nowak, 2015. "A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity," Nature, Nature, vol. 525(7568), pages 261-264, September.
    2. Andriy Marusyk & Doris P. Tabassum & Philipp M. Altrock & Vanessa Almendro & Franziska Michor & Kornelia Polyak, 2014. "Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity," Nature, Nature, vol. 514(7520), pages 54-58, October.
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    Cited by:

    1. Spouge, John L., 2019. "An accurate approximation for the expected site frequency spectrum in a Galton–Watson process under an infinite sites mutation model," Theoretical Population Biology, Elsevier, vol. 127(C), pages 7-15.
    2. Gunnarsson, Einar Bjarki & Leder, Kevin & Foo, Jasmine, 2021. "Exact site frequency spectra of neutrally evolving tumors: A transition between power laws reveals a signature of cell viability," Theoretical Population Biology, Elsevier, vol. 142(C), pages 67-90.

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