Nature Reviews Genetics 10, 336-342 (May 2009) | doi:10.1038/nrg2556

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

Amy Brock1,3, Hannah Chang1,3 & Sui Huang2  About the authors


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.

Author affiliations

  1. Amy Brock and Hannah Chang are at the Children's Hospital, Vascular Biology Program, Harvard Medical School, Boston, Massachusetts 02215, USA.
  2. Sui Huang is at the Institute for Biocomplexity and Informatics, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
  3. These authors contributed equally to this work.

Correspondence to: Sui Huang2 Email:


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