title: Spatial Measures of Genetic Heterogeneity During Carcinogenesis.
abstract: 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.
authors.affiliation: University of Minnesota Twin Cities, Minneapolis, MN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Storey
authors.affiliation: Department of Surgery, Division of Oncologic and GI Surgery, Duke University Medical Center, Durham, NC, USA.|Department of Mathematics, Duke University, Durham, NC, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Ryser
authors.affiliation: University of Minnesota Twin Cities, Minneapolis, MN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Leder
authors.affiliation: University of Minnesota Twin Cities, Minneapolis, MN, USA. jyfoo@umn.edu.
authors.forename: J
authors.initials: J
authors.lastname: Foo
mesh_terms: D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D003043:Cocarcinogenesis / Q000235:genetics / Q000473:pathology; D003198:Computer Simulation; D006801:Humans; D055641:Mathematical Concepts; D008957:Models, Genetic; D009010:Monte Carlo Method; D009154:Mutation; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics / Q000473:pathology; D013269:Stochastic Processes
keywords: Carcinogenesis; Genetic heterogeneity; Spatial evolution