Multifocality and recurrence risk: a quantitative model of field cancerization
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Abstract: Primary tumors often emerge within genetically altered fields of premalignant cells that appear histologically normal but have a high chance of progression to malignancy. Clinical observations have suggested that these premalignant fields pose high risks for emergence of secondary recurrent tumors if left behind after surgical removal of the primary tumor. In this work, we develop a spatio-temporal stochastic model of epithelial carcinogenesis, combining cellular reproduction and death dynamics with a general framework for multi-stage genetic progression to cancer. Using this model, we investigate how macroscopic features (e.g. size and geometry of premalignant fields) depend on microscopic cellular properties of the tissue (e.g. tissue renewal rate, mutation rate, selection advantages conferred by genetic events leading to cancer, etc). We develop methods to characterize how clinically relevant quantities such as waiting time until emergence of second field tumors and recurrence risk after tumor resection. We also study the clonal relatedness of recurrent tumors to primary tumors, and analyze how these phenomena depend upon specific characteristics of the tissue and cancer type. This study contributes to a growing literature seeking to obtain a quantitative understanding of the spatial dynamics in cancer initiation.
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Cited in
(5)- Spatial Moran models. II: Cancer initiation in spatially structured tissue
- Spread of premalignant mutant clones and cancer initiation in multilayered tissue
- A spatial mutation model with increasing mutation rates
- Mutation timing in a spatial model of evolution
- Spatial measures of genetic heterogeneity during carcinogenesis
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