Evolutionary dynamics of tumor progression with random fitness values.
Evolutionary dynamics of tumor progression with random fitness values.
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DOI：
10.1016/j.tpb.2010.05.001
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发表时间：
2010-08
影响因子：
1.4
通讯作者：
Michor, Franziska
中科院分区：
文献类型：
--
作者：
Durrett, Rick;Foo, Jasmine;Leder, Kevin;Mayberry, John;Michor, Franziska
关键词：
大多数人类肿瘤是由单个细胞中多种遗传和表观遗传改变的积累引起的。赋予细胞适应性优势的突变被称为驱动突变，并且与肿瘤发生有因果关系。然而，其他突变不会改变细胞的表型，甚至不会降低细胞的适应性。虽然许多实验努力致力于识别个体突变的功能效应，但肿瘤进展的数学建模通常考虑随着突变的累积而恒定的适应性增量。本文研究了具有随机适应度增量的肿瘤发展数学模型。我们分析了一个多类型的分支过程中，细胞积累的突变，其健身效果是从分布中选择。我们确定的适应度分布对肿瘤的生长动力学的影响。这项工作有助于定量了解导致癌症的突变的积累。
Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis. Other mutations, however, do not change the phenotype of the cell or even decrease cellular fitness. While much experimental effort is being devoted to the identification of the functional effects of individual mutations, mathematical modeling of tumor progression generally considers constant fitness increments as mutations are accumulated. In this paper we study a mathematical model of tumor progression with random fitness increments. We analyze a multi-type branching process in which cells accumulate mutations whose fitness effects are chosen from a distribution. We determine the effect of the fitness distribution on the growth kinetics of the tumor. This work contributes to a quantitative understanding of the accumulation of mutations leading to cancer.
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通讯作者：
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