SPREAD OF PREMALIGNANT MUTANT CLONES AND CANCER INITIATION IN MULTILAYERED TISSUE

• 成果类型: Article
• 署名作者: Foo, Jasmine; Gunnarsson, Einar Bjarki; Leder, Kevin; Storey, Kathleen
• 署名单位: University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Lafayette College
• 刊物名称: ANNALS OF APPLIED PROBABILITY
• ISSN/ISSBN: 1050-5164
• DOI: 10.1214/22-AAP1816
• 发表日期: 2023
• 页码: 299-343
• 关键词: spatial moran models; GROWTH; Mutation

摘要

Over 80% of human cancers originate from the epithelium, which covers the outer and inner surfaces of organs and blood vessels. In stratified epithe-lium, the bottom layers are occupied by stem and stem-like cells that contin-ually 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.