SPREAD OF PREMALIGNANT MUTANT CLONES AND CANCER INITIATION IN MULTILAYERED TISSUE
SPREAD OF PREMALIGNANT MUTANT CLONES AND CANCER INITIATION IN MULTILAYERED TISSUE
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DOI：
10.1214/22-aap1816
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发表时间：
2023-02-01
影响因子：
1.8
通讯作者：
Storey, Kathleen
中科院分区：
文献类型：
--
作者：
Foo, Jasmine;Gunnarsson, Einar Bjarki;Storey, Kathleen
超过80%的人类癌症起源于覆盖器官和血管内外表面的上皮。在分层上皮中，底层被干细胞和干细胞样细胞占据，干细胞和干细胞样细胞不断分裂并补充上层。在这项工作中，我们研究了癌前突变克隆在分层上皮中的扩散和癌症的发生，使用了堆叠二维晶格上的有偏选民模型。我们的主要结果是对癌前突变克隆的繁殖速度的估计，它在癌症相关的弱选择极限中是渐进精确的。我们使用我们的主要结果来研究癌症两步突变模型下的癌症起始，其中包括计算癌症起始时间的分布和引起癌症的癌前克隆的大小。我们的工作量化了上皮组织厚度对癌变过程的影响，从而有助于对癌症的空间进化动力学的新兴理解。
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.