Exploring the relationship between neutral and selective mutations in cancer

被引:27
作者
Maley, CC
Forrest, S
机构
[1] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
[2] Univ New Mexico, Dept Comp Sci, Albuquerque, NM 87131 USA
[3] Santa Fe Inst, Santa Fe, NM 87501 USA
关键词
cancer; progression; mutator phenotype; agent-based model; evolution;
D O I
10.1162/106454600300103665
中图分类号
TP18 [人工智能理论];
学科分类号
081104 ; 0812 ; 0835 ; 1405 ;
摘要
The transformation of normal cells into cancerous cells is an evolutionary process. Populations of precancerous cells reproduce, mutate, and compete for resources. Some of these mutations eventually lead to cancer. We calculate the probability of developing cancer under a set of simplifying assumptions and then elaborate these calculations, culminating in a simple simulation of the cell dynamics. The agent-based model allows us to examine the interactions of mutations critical for the development of cancer that are either evolutionarily neutral or selective. We an also examine the interaction of these mutations with a "mutator phenotype" derived from mutation that raise the mutation rate for the entire cell. The simulation suggest that there must be at least two selectively neutral mutations necessary for th development of cancer and that preventive treatments will be most effective when they increase this number. The model also suggests that selective mutations facilitate the development of cancer, so that the more selective mutations necessary for the development of cancer, the greater the chance of developing it.
引用
收藏
页码:325 / 345
页数:21
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