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The causes and consequences of genetic heterogeneity in cancer evolution

Abstract

Recent studies have revealed extensive genetic diversity both between and within tumours. This heterogeneity affects key cancer pathways, driving phenotypic variation, and poses a significant challenge to personalized cancer medicine. A major cause of genetic heterogeneity in cancer is genomic instability. This instability leads to an increased mutation rate and can shape the evolution of the cancer genome through a plethora of mechanisms. By understanding these mechanisms we can gain insight into the common pathways of tumour evolution that could support the development of future therapeutic strategies.

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Figure 1: Intertumour and intratumour heterogeneity.

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Acknowledgements

We would like to apologize to those whose work we have not been able to cite owing to space limitations. C.S. is funded by Cancer Research UK, The Medical Research Council, EU FP7 (projects PREDICT and RESPONSIFY), Prostate Cancer Foundation and the Breast Cancer Research Foundation (BCRF). J.B. is funded by the Danish Cancer Society and the European Commission (projects DDResponse and Biomedreg). We thank E. Grönroos and P. Gorman for the use of the tumour section image in Fig. 1.

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Burrell, R., McGranahan, N., Bartek, J. et al. The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501, 338–345 (2013). https://doi.org/10.1038/nature12625

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