Cell
Volume 166, Issue 5, 25 August 2016, Pages 1132-1146.e7
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Article
Multi-organ Mapping of Cancer Risk

https://doi.org/10.1016/j.cell.2016.07.045Get rights and content
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Highlights

  • Prom1+ cells display different generative and tumorigenic capacities among organs

  • Prom1+ cell transformation is determined by life-long generative capacity

  • Prom1 marks neonatal liver and damage-induced adult liver stem cells

  • Stem cell gene expression patterns predict oncogenes and tumor suppressors

Summary

Cancers are distributed unevenly across the body, but the importance of cell intrinsic factors such as stem cell function in determining organ cancer risk is unknown. Therefore, we used Cre-recombination of conditional lineage tracing, oncogene, and tumor suppressor alleles to define populations of stem and non-stem cells in mouse organs and test their life-long susceptibility to tumorigenesis. We show that tumor incidence is determined by the life-long generative capacity of mutated cells. This relationship held true in the presence of multiple genotypes and regardless of developmental stage, strongly supporting the notion that stem cells dictate organ cancer risk. Using the liver as a model system, we further show that damage-induced activation of stem cell function markedly increases cancer risk. Therefore, we propose that a combination of stem cell mutagenesis and extrinsic factors that enhance the proliferation of these cell populations, creates a “perfect storm” that ultimately determines organ cancer risk.

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