Spatial Measures of Genetic Heterogeneity During Carcinogenesis

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• 作者：K. Storey ; M. D. Ryser ; K. Leder ; J. Foo
• 关键词：Carcinogenesis ; Spatial evolution ; Genetic heterogeneity
• 刊名：Bulletin of Mathematical Biology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：79
• 期：2
• 页码：237-276
• 全文大小：
• 刊物类别：Mathematics and Statistics
• 刊物主题：Mathematical and Computational Biology; Life Sciences, general; Cell Biology;
• 出版者：Springer US
• ISSN：1522-9602
• 卷排序：79

文摘

In this work we explore the temporal dynamics of spatial heterogeneity during the process of tumorigenesis from healthy tissue. We utilize a spatial stochastic model of mutation accumulation and clonal expansion in a structured tissue to describe this process. Under a two-step tumorigenesis model, we first derive estimates of a non-spatial measure of diversity: Simpson’s Index, which is the probability that two individuals sampled at random from the population are identical, in the premalignant population. We next analyze two new measures of spatial population heterogeneity. In particular we study the typical length scale of genetic heterogeneity during the carcinogenesis process and estimate the extent of a surrounding premalignant clone given a clinical observation of a premalignant point biopsy. This evolutionary framework contributes to a growing literature focused on developing a better understanding of the spatial population dynamics of cancer initiation and progression.