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Breast cancer

Subclones—go forth and mutate

Nature Reviews Clinical Oncology volume 11, page 560 (2014)Cite this article

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A novel DNA-sequencing method, Nuc-Seq, has been used for single-cell analysis of cells isolated from one oestrogen-receptor positive (ER+) breast tumour and one triple-negative breast cancer (TNBC), with coverage of >90% of the whole genome. “Our data clearly show that no two single tumour cells are genetically identical, challenging the strict definition of 'clones' as 'genetically identical cells',” claims Nicholas Navin, who led the study.

Initial copy-number profiling revealed that cells within each tumour shared chromosomal abnormalities, suggesting that such aberrations evolve in punctuated bursts followed by stable clonal expansions to form a monoclonal tumour mass. “By contrast, we found that the evolution of point mutations occurs gradually over long periods of time, generating extensive clonal diversity,” explains Navin. The Nuc-Seq data, validated by deep sequencing, identified many subclonal and de novo point mutations at low frequencies in the tumour mass, often present in <1% of cells, and in only 0.01% of cells for some. “These rare subclonal mutations may play an important part in diversifying the phenotypes of cancer cells when they are challenged by selective pressures in the tumour microenvironment, including perhaps the greatest pressure of all: chemotherapy.”

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References

  1. Wang, Y. et al. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature 10.1038/nature13600

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  1. David Killock
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Killock, D. Subclones—go forth and mutate. Nat Rev Clin Oncol 11, 560 (2014). https://doi.org/10.1038/nrclinonc.2014.140

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