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Selection and adaptation during metastatic cancer progression

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Abstract

Cancer is often regarded as a process of asexual evolution driven by genomic and genetic instability. Mutation, selection and adaptation are by convention thought to occur primarily within, and to a lesser degree outside, the primary tumour. However, disseminated cancer cells that remain after 'curative' surgery exhibit extreme genomic heterogeneity before the manifestation of metastasis. This heterogeneity is later reduced by selected clonal expansion, suggesting that the disseminated cells had yet to acquire key traits of fully malignant cells. Abrogation of the cells' progression outside the primary tumour implies new challenges and opportunities for diagnosis and adjuvant therapies.

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Figure 1: Mutations in benign tumours.
Figure 2: Macroevolution and microevolution of breast cancer genomes.
Figure 3: Early steps of metastasis at ectopic sites in bone marrow.
Figure 4: Heterogeneity of metastasis and homogenization by systemic therapies.

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Acknowledgements

I am indebted to T. Perry for his critical reading of the manuscript and his invaluable suggestions to improve it. I am also grateful to S. Pausch for her help with the figures.

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Klein, C. Selection and adaptation during metastatic cancer progression. Nature 501, 365–372 (2013). https://doi.org/10.1038/nature12628

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