Modeling the subclonal evolution of cancer cell populations

Diego Chowell, James Napier, Rohan Gupta, Karen Anderson, Carlo Maley, Melissa Wilson Sayres

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 strongly with the number of subclones (<10% of the tumor). Overall, these subclones were frequently below current standard detection thresholds, frequently harbored treatment-resistant mutations, and were more common in slow-growing tumors. Significance: The model presented in this paper addresses tumor heterogeneity by framing expectations for the number of resistant subclones in a tumor, with implications for future studies of the evolution of therapeutic resistance.

Original languageEnglish (US)
Pages (from-to)830-839
Number of pages10
JournalCancer Research
Volume78
Issue number3
DOIs
StatePublished - Feb 1 2018

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Population
Neoplasms
Clone Cells
Genetic Drift
Mutation
Population Genetics
Glioblastoma
Colorectal Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Modeling the subclonal evolution of cancer cell populations. / Chowell, Diego; Napier, James; Gupta, Rohan; Anderson, Karen; Maley, Carlo; Wilson Sayres, Melissa.

In: Cancer Research, Vol. 78, No. 3, 01.02.2018, p. 830-839.

Research output: Contribution to journalArticle

Chowell, Diego ; Napier, James ; Gupta, Rohan ; Anderson, Karen ; Maley, Carlo ; Wilson Sayres, Melissa. / Modeling the subclonal evolution of cancer cell populations. In: Cancer Research. 2018 ; Vol. 78, No. 3. pp. 830-839.
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