Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/105345
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Type: Journal article
Title: Differential clonal expansion in an invading cell population: clonal advantage or dumb luck?
Author: Newgreen, D.
Zhang, D.
Cheeseman, B.
Binder, B.
Landman, K.
Citation: Cells Tissues Organs, 2017; 203(2):105-113
Publisher: Karger
Issue Date: 2017
ISSN: 1422-6405
1422-6421
Statement of
Responsibility: 
D.F. Newgreen, D. Zhang, B.L. Cheeseman, B.J. Binder, K.A. Landman
Abstract: In neoplastic cell growth, clones and subclones are variable both in size and mutational spectrum. The largest of these clones are believed to represent those cells with mutations that make them the most "fit," in a Darwinian sense, for expansion in their microenvironment. Thus, the degree of quantitative clonal expansion is regarded as being determined by innate qualitative differences between the cells that originate each clone. Here, using a combination of mathematical modelling and clonal labelling experiments applied to the developmental model system of the forming enteric nervous system, we describe how cells which are qualitatively identical may consistently produce clones of dramatically different sizes: most clones are very small while a few clones we term "superstars" contribute most of the cells to the final population. The basis of this is minor stochastic variations ("luck") in the timing and direction of movement and proliferation of individual cells, which builds a local advantage for daughter cells that is cumulative. This has potentially important consequences. In cancers, especially before strongly selective cytotoxic therapy, the assumption that the largest clones must be the cells with deterministic proliferative ability may not always hold true. In development, the gradual loss of clonal diversity as "superstars" take over the population may erode the resilience of the system to somatic mutations, which may have occurred early in clonal growth.
Keywords: Clonal growth; stochasticity; neoplasia; neural crest; enteric nervous system; cell motility; cell proliferation; mathematical modelling; cellular automata
Rights: © 2017 S. Karger AG, Basel
RMID: 0030066021
DOI: 10.1159/000452793
Grant ID: http://purl.org/au-research/grants/nhmrc/1069757
Appears in Collections:Medicine publications

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