■最近的研究表明,随着年龄的增长,正常人组织会积累大量的体细胞突变,达到与其相应癌症相当的水平。如果突变导致癌症,当突变不可避免时,组织如何避免癌症?
■小肠(SI)和结肠积累了相似数量的复制错误,但是SI腺癌比结直肠癌罕见得多。小肠和大肠都被细分为数百万个由少量干细胞维持的小社区(隐窝)。为了解释SI癌症悖论,四个基本进化参数(突变,漂移,选择,和人口规模)被翻译成隐窝。
■单个干细胞中驱动突变的积累可能类似于进化扑克游戏。SI癌的罕见性可能反映了SI隐窝比结肠更小,干细胞更少,这减少了有突变风险的细胞数量,并可能减少了选择效率。组织微结构可以通过控制直接竞争的相邻细胞的数量来物理调节癌症的进化。对SI癌症悖论的更好理解可以阐明当突变不可避免时组织如何自然避免癌症。
UNASSIGNED: Recent studies demonstrate that normal human tissues accumulate substantial numbers of somatic mutations with aging, to levels comparable to their corresponding cancers. If mutations cause cancer, how do tissues avoid cancer when mutations are unavoidable?
UNASSIGNED: The small intestines (SI) and colon accumulate similar numbers of replication errors, but SI adenocarcinoma is much rarer than colorectal cancer. Both the small and large intestines are subdivided into millions of small neighborhoods (crypts) that are maintained by small numbers of stem cells. To explain the SI cancer paradox, four fundamental evolution parameters (mutation, drift, selection, and population size) are translated to crypts.
UNASSIGNED: The accumulations of driver mutations in a single stem cell may be analogous to an evolutionary poker game. The rarity of SI cancer may reflect that SI crypts are smaller and have fewer stem cells than the colon, which reduces the numbers of cells at risk for mutation and perhaps selection efficiency. Tissue microarchitecture may physically modulate cancer evolution by controlling the numbers of directly competing neighboring cells. A better understanding of the SI cancer paradox may illuminate how tissues naturally avoid cancers when mutations are unavoidable.