Population mutation properties of tumor evolution
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ORIGINAL PAPER
Population mutation properties of tumor evolution LeeYoung Park1 Received: 15 July 2020 / Accepted: 15 September 2020 / Published online: 25 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Tumor growth patterns differ depending on the individual tumor, leading to various patterns of genetic heterogeneity across tumors. Despite their importance, the population mutation properties of tumor evolution have not been well studied, especially in terms of overall genetic heterogeneity. The current study aims to examine factors in tumor evolution influencing overall genetic heterogeneity. Extensive simulations of the representative evolutionary patterns of various tumors were conducted in the current study to determine the overall genetic characteristics of tumor evolution. The variations in cell birth/death rates and angiogenesis duration were examined based on the simplest growth pattern of tumors with avascular growth, angiogenesis, and vascular growth. To examine the impact of evolutionary tree structure, three-step linear evolution and branching evolution were investigated based on various subpopulation initiation times. The population size during the initial growth phase and the duration of angiogenesis are important factors affecting overall genetic heterogeneity. Furthermore, the shape of the evolutionary tree is crucial for defining the genetic heterogeneity of the extant tumor cell population, indicating the importance of the initiation timing of subpopulations. Branching evolution results in slightly greater genetic heterogeneity in terms of allelic distribution than in terms of the number of variants. The results of the current study reveal that the pattern of tumor evolution is critical for defining tumor genetic heterogeneity. These population genetic approaches are important for understanding the properties of tumor cell populations. Keywords Tumor evolution · Simulation · Genetic heterogeneity · Population mutation parameter · Linear growth · Branching growth Abbreviation θ Population mutation parameter
Introduction Tumors develop from a single cell via serial mutation events [1, 2], except under special conditions [3], which inevitably results in heterogeneity among tumor cell populations [4]. Recent efforts based on single-cell technology have highlighted this heterogeneity, as it critically influences tumor cell survival and metastasis [5–7]. Each tumor is unique in its developmental process and background genetics [8, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12032-020-01421-6) contains supplementary material, which is available to authorized users. * LeeYoung Park [email protected] 1
Natural Science Research Institute, Yonsei University, Yonsei‑ro 50, Seodaemun‑Gu, Seoul 03722, Korea
9]. Certain tumor types share specific dysregulated genes, enabling targeting common pathways for anti-cancer therapeutics [10, 11]. However, each tumor has unique mutations in companion with the
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