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Cancer risk

Generating tumours: it's all in the balance

Nature Reviews Cancer volume 16, page 753 (2016)Cite this article

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There is debate about the influence of intrinsic and extrinsic factors (such as exposure to carcinogens) that drive tumorigenesis and thus influence cancer incidence in an organ-specific and age-associated manner. An important intrinsic risk factor has been proposed to arise from the accumulation over time of random mutations that result from errors in stem cell division. Extrinsic factors may also influence the accumulation of mutations and thus cancer risk.

Next, the authors introduced various conditional oncogenic mutations, resulting in 316 tumours in 280 mice. Interestingly, few or no tumours developed in the salivary gland, kidney, brain or pancreas. Some PROM1+ cell populations were more susceptible than others to transformation, regardless of the oncogenic mutations that were introduced. Mathematical modelling was used to assess whether PROM1+ cell population size, proliferative capacity and/or generative capacity are related to tumorigenesis in each organ. They found that generative capacity correlated with susceptibility to tumorigenesis, such that organs with the smallest PROM1+ cell populations were the most likely to develop tumours.

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References

  1. Blokzijl, F. et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538, 260–264 (2016)

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  2. Zhu, L. et al. Multi-organ mapping of cancer risk. Cell 166, 1132–1146 (2016)

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Authors
  1. Gemma K. Alderton
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Alderton, G. K. Debating the odds. Nat. Rev. Cancer 16, 68 (2016)

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Alderton, G. Generating tumours: it's all in the balance. Nat Rev Cancer 16, 753 (2016). https://doi.org/10.1038/nrc.2016.137

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