Evolutionary dynamics of tumor progression with random fitness values

TL;DR

This paper introduces a mathematical model of tumor progression where mutations confer random fitness effects, analyzing how these stochastic fitness increments influence tumor growth dynamics.

Contribution

It develops a novel multi-type branching process model incorporating random fitness effects, advancing understanding of mutation accumulation in cancer development.

Findings

Fitness distribution significantly affects tumor growth rate

Random fitness effects lead to diverse tumor progression trajectories

Model provides a quantitative framework for mutation accumulation in cancer

Abstract

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 different 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 phenotypes.