Clonal evolution driven by superdriver mutations
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 numb...
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | BMC Evolutionary Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12862-020-01647-y |
| _version_ | 1819131174702809088 |
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| author | Patrick Grossmann Simona Cristea Niko Beerenwinkel |
| author_facet | Patrick Grossmann Simona Cristea Niko Beerenwinkel |
| author_sort | Patrick Grossmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T09:11:19Z |
| format | Article |
| id | doaj.art-d2c7a8558f2e44a7b33d154775aa3e90 |
| institution | Directory Open Access Journal |
| issn | 1471-2148 |
| language | English |
| last_indexed | 2024-12-22T09:11:19Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Evolutionary Biology |
| spelling | doaj.art-d2c7a8558f2e44a7b33d154775aa3e902022-12-21T18:31:26ZengBMCBMC Evolutionary Biology1471-21482020-07-0120111110.1186/s12862-020-01647-yClonal evolution driven by superdriver mutationsPatrick Grossmann0Simona Cristea1Niko Beerenwinkel2Department of Biosystems Science and Engineering, ETH ZurichDepartment of Biostatistics & Computational Biology, Dana-Farber Cancer InstituteDepartment of Biosystems Science and Engineering, ETH ZurichAbstract 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.http://link.springer.com/article/10.1186/s12862-020-01647-yCancer progressionTumorigenesisMutationSelectionFitnessWaiting time to cancer |
| spellingShingle | Patrick Grossmann Simona Cristea Niko Beerenwinkel Clonal evolution driven by superdriver mutations BMC Evolutionary Biology Cancer progression Tumorigenesis Mutation Selection Fitness Waiting time to cancer |
| title | Clonal evolution driven by superdriver mutations |
| title_full | Clonal evolution driven by superdriver mutations |
| title_fullStr | Clonal evolution driven by superdriver mutations |
| title_full_unstemmed | Clonal evolution driven by superdriver mutations |
| title_short | Clonal evolution driven by superdriver mutations |
| title_sort | clonal evolution driven by superdriver mutations |
| topic | Cancer progression Tumorigenesis Mutation Selection Fitness Waiting time to cancer |
| url | http://link.springer.com/article/10.1186/s12862-020-01647-y |
| work_keys_str_mv | AT patrickgrossmann clonalevolutiondrivenbysuperdrivermutations AT simonacristea clonalevolutiondrivenbysuperdrivermutations AT nikobeerenwinkel clonalevolutiondrivenbysuperdrivermutations |