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Mathematics > Probability

arXiv:2007.03366 (math)
[Submitted on 7 Jul 2020 (v1), last revised 26 Mar 2022 (this version, v2)]

Title:Spread of premalignant mutant clones and cancer initiation in multilayered tissue

Authors:Jasmine Foo, Einar Bjarki Gunnarsson, Kevin Leder, Kathleen Storey
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Abstract: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.
Comments: 49 pages, 11 figures, accepted for publication in Annals of Applied Probability
Subjects: Probability (math.PR); Populations and Evolution (q-bio.PE)
MSC classes: 60G50, 60J27, 60K35, 92B05, 92C50, 92D25
Cite as: arXiv:2007.03366 [math.PR]
  (or arXiv:2007.03366v2 [math.PR] for this version)
  https://doi.org/10.48550/arXiv.2007.03366
Journal reference: Annals of Applied Probability 33(1) (2023) 299-343
Related DOI: https://doi.org/10.1214/22-AAP1816

Submission history

From: Einar Bjarki Gunnarsson [view email]
[v1] Tue, 7 Jul 2020 11:56:55 UTC (646 KB)
[v2] Sat, 26 Mar 2022 21:01:22 UTC (817 KB)
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