Spread of premalignant mutant clones and cancer initiation in multilayered tissue

Over 80% of human cancers originate from the epithelium, which covers the outer and inner surfaces of organs and blood vessels. In stratified epithelium, the bottom layers are occupied by stem and stem-like cells that continually divide and replenish the upper layers. In this work, we study the spread of premalignant mutant clones and cancer initiation in stratified epithelium, using the biased voter model on stacked two-dimensional lattices. Our main result is an estimate of the propagation speed of a premalignant mutant clone, which is asymptotically precise in the cancer-relevant weak-selection limit. We use our main result to study cancer initiation under a two-step mutational model of cancer, which includes computing the distributions of the time of cancer initiation and the size of the premalignant clone giving rise to cancer. Our work quantifies the effect of epithelial tissue thickness on the process of carcinogenesis, thereby contributing to an emerging understanding of the spatial evolutionary dynamics of cancer.

Title	Spread of premalignant mutant clones and cancer initiation in multilayered tissue
Creator	Storey, Kathleen M.
	Gunnarsson, E. B.
	Foo, J.
	Leder, K.
Publisher	Annals of Applied Probability
Academic Department	Mathematics
Division	Natural Sciences
Organization	Lafayette College
Date Issued	February 2023
Date Available	2023-05-09
Type	Article
Language	English
Keyword	Spatial cancer models
	biased voter model
	branching coalescing random walks
	field cancerization
	evolutionary dynamics
Bibliographic Citation	Foo, J., et al. (2023 Feb) "Spread of premalignant mutant clones and cancer initiation in multilayered tissue." Annals of Applied Probability 33 (1): 299-343.
Standard Identifier	Handle 10385/zg64tn714
Standard Identifier	DOI 10.1214/22-AAP1816
Permalink	http://hdl.handle.net/10385/zg64tn714
Rights Statement	In Copyright
Rights Holders	Institute of Mathematical Statistics