作者
Diego Chowell, James Napier, Rohan Gupta, Karen S Anderson, Carlo C Maley, Melissa A Wilson Sayres
发表日期
2018/2/1
期刊
Cancer research
卷号
78
期号
3
页码范围
830-839
出版商
American Association for Cancer Research
简介
Increasing evidence shows that tumor clonal architectures are often the consequence of a complex branching process, yet little is known about the expected dynamics and extent to which these divergent subclonal expansions occur. Here, we develop and implement more than 88,000 instances of a stochastic evolutionary model simulating genetic drift and neoplastic progression. Under different combinations of population genetic parameter values, including those estimated for colorectal cancer and glioblastoma multiforme, the distribution of sizes of subclones carrying driver mutations had a heavy right tail at the time of tumor detection, with only 1 to 4 dominant clones present at ≥10% frequency. In contrast, the vast majority of subclones were present at <10% frequency, many of which had higher fitness than currently dominant clones. The number of dominant clones (≥10% frequency) in a tumor correlated …
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D Chowell, J Napier, R Gupta, KS Anderson, CC Maley… - Cancer research, 2018