Clonal evolution driven by superdriver mutations.

IF 3.4 Q1 Agricultural and Biological Sciences
Patrick Grossmann, Simona Cristea, Niko Beerenwinkel
{"title":"Clonal evolution driven by superdriver mutations.","authors":"Patrick Grossmann,&nbsp;Simona Cristea,&nbsp;Niko Beerenwinkel","doi":"10.1186/s12862-020-01647-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9111,"journal":{"name":"BMC Evolutionary Biology","volume":"20 1","pages":"89"},"PeriodicalIF":3.4000,"publicationDate":"2020-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12862-020-01647-y","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Evolutionary Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s12862-020-01647-y","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Agricultural and Biological Sciences","Score":null,"Total":0}
引用次数: 4

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.

Abstract Image

Abstract Image

Abstract Image

由超级驱动突变驱动的克隆进化。
背景:肿瘤被广泛认为是通过克隆进化,依次获得选择性有利的遗传改变,从而显著促进肿瘤的发生,因此被称为驱动因素。一些癌症驱动因素,如TP53点突变或EGFR拷贝数增加,提供了特殊的适应性增加,这在时间上足以触发癌症的发作,而很少或没有其他遗传改变的贡献。这些关键的变化被称为超级驱动程序。结果:在本研究中,我们采用Wright-Fisher模型来研究肿瘤进展中驱动因子和超级驱动因子之间的相互作用。我们证明了由此产生的进化动力学遵循超驱动器的全局克隆扩展和驱动器的周期性克隆扩展。我们发现肿瘤细胞群中一组超驱动因子和驱动因子累积的等待时间可以近似为个体等待时间的总和。结论:我们的研究结果表明,在肿瘤发生过程中,超级驱动动力学比驱动动力学起主导作用。此外,我们的模型允许从经验和理论上研究超级驱动程序和驱动程序突变之间的相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
BMC Evolutionary Biology
BMC Evolutionary Biology 生物-进化生物学
CiteScore
5.80
自引率
0.00%
发文量
0
审稿时长
6 months
期刊介绍: BMC Evolutionary Biology is an open access, peer-reviewed journal that considers articles on all aspects of molecular and non-molecular evolution of all organisms, as well as phylogenetics and palaeontology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信