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Cells of origin in cancer

Abstract

Both solid tumours and leukaemias show considerable histological and functional heterogeneity. It is widely accepted that genetic lesions have a major role in determining tumour phenotype, but evidence is also accumulating that cancers of distinct subtypes within an organ may derive from different 'cells of origin'. These cells acquire the first genetic hit or hits that culminate in the initiation of cancer. The identification of these crucial target cell populations may allow earlier detection of malignancies and better prediction of tumour behaviour, and ultimately may lead to preventive therapies for individuals at high risk of developing cancer.

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Figure 1: The cell of origin and evolution of a cancer stem cell.
Figure 2: Two models of intertumoral heterogeneity.
Figure 3: Strategies used to identify cells of origin in cancer.
Figure 4: Identification of crypt stem cells as the cell of origin in intestinal cancer by lineage tracing.

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Acknowledgements

I am grateful to J. Adams, G. Lindeman and A. Strasser for critical review of the manuscript, P. Dirks for discussion and P. Maltezos for preparation of figures. I apologize to authors whose work could not be cited owing to space limitations. J.E.V. is supported by the National Health and Medical Research Council and the Victorian Breast Cancer Research Consortium.

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Visvader, J. Cells of origin in cancer. Nature 469, 314–322 (2011). https://doi.org/10.1038/nature09781

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