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Clonal evolution of colorectal cancer in IBD

Key Points

  • Colorectal cancer development in IBD begins many years before the development of neoplasia because of occult evolution within the inflamed bowel

  • The cycles of wounding and repair characteristic of IBD provide a selective pressure for mutant cells that are able to rapidly heal the mucosa and withstand the inflammatory insult

  • Measuring and modulating the occult evolutionary process offers new avenues for effectively predicting and preventing colorectal cancer in IBD

  • Repositories of IBD surveillance materials offer a surreptitious opportunity to study in vivo clonal evolution in time and space in humans

Abstract

Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.

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Figure 1: Differences in clonal expansion between normal and inflamed mucosa.
Figure 2: Different potential manifestations of mutant clonal evolution in IBD.

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Acknowledgements

The authors are grateful for funding from Cancer Research UK, the Medical Research Council, the Derek Willoughby Fund for Inflammatory Research, the St Mark's Hospital Foundation and Barts Charity.

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The authors contributed equally to the review.

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Correspondence to Chang-Ho R. Choi, Ibrahim Al Bakir, Ailsa L. Hart or Trevor A. Graham.

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Choi, CH., Bakir, I., Hart, A. et al. Clonal evolution of colorectal cancer in IBD. Nat Rev Gastroenterol Hepatol 14, 218–229 (2017). https://doi.org/10.1038/nrgastro.2017.1

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