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Non-genetic heterogeneity — a mutation-independent driving force for the somatic evolution of tumours

Nature Reviews Genetics volume 10, pages 336–342 (2009)Cite this article

Abstract

Clonal populations of mammalian cells are inherently heterogeneous. They contain cells that display non-genetic variability resulting from gene expression noise and the fact that gene networks have multiple stable states. These stable, heritable variants within one cell type can exhibit different levels of responsiveness to environmental conditions. Hence, they could in principle serve as a temporary substrate for natural selection in the absence of mutations. We suggest that such ubiquitous but non-genetic variability can contribute to the somatic evolution of cancer cells, hence accelerating tumour progression independently of genetic mutations.

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Figure 1: Flow cytometry reveals heterogeneity of phenotype in a clonal cell population.
Figure 2: A model of non-genetic population evolution of drug-resistant clones in cancer progression.

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Acknowledgements

S.H. acknowledges support from the Air Force Office of Scientific Research, the National Institutes of Health and the Canada Foundation of Innovation. The authors also thank Alfonso Martinez-Arias for many discussions.

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Author notes

  1. Amy Brock and Hannah Chang: These authors contributed equally to this work.

Authors and Affiliations

  1. Amy Brock and Hannah Chang are at the Children's Hospital, Vascular Biology Program, Harvard Medical School, Boston, Massachusetts 02215, USA.,

    Amy Brock & Hannah Chang

  2. Sui Huang is at the Institute for Biocomplexity and Informatics, University of Calgary, Calgary, Alberta T2N 1N4, Canada.,

    Sui Huang

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  1. Amy Brock
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Correspondence to Sui Huang.

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Brock, A., Chang, H. & Huang, S. Non-genetic heterogeneity — a mutation-independent driving force for the somatic evolution of tumours. Nat Rev Genet 10, 336–342 (2009). https://doi.org/10.1038/nrg2556

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