Spread of premalignant mutant clones and cancer initiation in multilayered tissue

TL;DR

This paper models the spread of premalignant clones in stratified epithelium using a biased voter model, providing estimates of clone propagation speed and insights into how tissue thickness influences cancer initiation.

Contribution

It introduces a mathematical framework for understanding premalignant clone spread in multilayered tissue, including precise propagation speed estimates and cancer initiation timing.

Findings

Propagation speed of premalignant clones estimated in weak-selection limit

Distribution of cancer initiation times computed

Tissue thickness impacts carcinogenesis dynamics

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.