Clonal evolution driven by superdriver mutations

BMC Evolutionary Biology

Simona Cristea¹  Patrick Grossmann²  Niko Beerenwinkel² 

[1] Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute;Department of Biosystems Science and Engineering, ETH Zurich;

关键词: Cancer progression;    Tumorigenesis;    Mutation;    Selection;    Fitness;    Waiting time to cancer;   

DOI  :  10.1186/s12862-020-01647-y

来源: DOAJ

【 摘 要 】

Abstract Background Tumors are widely recognized to progress through clonal evolution by sequentially acquiring selectively advantageous genetic alterations that significantly contribute to tumorigenesis and thus are termned drivers. Some cancer drivers, such as TP53 point mutation or EGFR copy number gain, provide exceptional fitness gains, which, in time, can be sufficient to trigger the onset of cancer with little or no contribution from additional genetic alterations. These key alterations are called superdrivers. Results In this study, we employ a Wright-Fisher model to study the interplay between drivers and superdrivers in tumor progression. We demonstrate that the resulting evolutionary dynamics follow global clonal expansions of superdrivers with periodic clonal expansions of drivers. We find that the waiting time to the accumulation of a set of superdrivers and drivers in the tumor cell population can be approximated by the sum of the individual waiting times. Conclusions Our results suggest that superdriver dynamics dominate over driver dynamics in tumorigenesis. Furthermore, our model allows studying the interplay between superdriver and driver mutations both empirically and theoretically.

【 授权许可】

Unknown