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A bacterial mutational footprint in colorectal cancer genomes

British Journal of Cancer volume 124, pages 1751–1753 (2021)Cite this article

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Summary

Changes in the microbiome are associated with the development of colorectal cancer, but causal explanations have been lacking. We recently demonstrated that pks+ Escherichia coli induce a specific mutational pattern using intestinal organoids and these mutations are present in the genomes of colorectal cancer. This finding warrants further studies on the microbial role in oncogenic mutation induction, cancer development and future preventive strategies.

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Fig. 1: pks+ mutational signatures in intestinal organoids and CRC.

References

  1. Nougayrède, J.-P., Homburg, S., Taieb, F., Boury, M., Brzuszkiewicz, E., Gottschalk, G. et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313, 848–851 (2006).

    Article  Google Scholar 

  2. Arthur, J. C., Perez-Chanona, E., Mühlbauer, M., Tomkovich, S., Uronis, J. M., Fan, T.-J. et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338, 120–123 (2012).

    Article  CAS  Google Scholar 

  3. Dejea, C. M., Fathi, P., Craig, J. M., Boleij, A., Taddese, R., Geis, A. L. et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359, 592–597 (2018).

    Article  CAS  Google Scholar 

  4. Alexandrov, L. B., Kim, J., Haradhvala, N. J., Huang, M. N., Tian Ng, A. W., Wu, Y. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94–101 (2020).

    Article  CAS  Google Scholar 

  5. Pleguezuelos-Manzano, C., Puschhof, J., Rosendahl Huber, A., van Hoeck, A., Wood, H. M., Nomburg, J. et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature 580, 269–273 (2020).

    Article  CAS  Google Scholar 

  6. Wilson, M. R., Jiang, Y., Villalta, P. W., Stornetta, A., Boudreau, P. D., Carrá, A. et al. The human gut bacterial genotoxin colibactin alkylates DNA. Science 363, eaar7785 (2019).

  7. Xue, M., Kim, C. S., Healy, A. R., Wernke, K. M., Wang, Z., Frischling, M. C. et al. Structure elucidation of colibactin and its DNA cross-links. Science 365, eaax2685 (2019).

  8. Terlouw, D., Suerink, M., Boot, A., Wezel, T., van, Nielsen, M. & Morreau, H. Recurrent APC splice variant c.835-8A>G in patients with unexplained colorectal polyposis fulfilling the colibactin mutational signature. Gastroenterology 159, 1612.e5–1614.e5 (2020).

    Article  Google Scholar 

  9. Lee-Six, H., Olafsson, S., Ellis, P., Osborne, R. J., Sanders, M. A., Moore, L. et al. The landscape of somatic mutation in normal colorectal epithelial cells. Nature 574, 532–537 (2019).

    Article  CAS  Google Scholar 

  10. Olafsson, S., McIntyre, R. E., Coorens, T., Butler, T., Jung, H., Robinson, P. S. et al. Somatic evolution in non-neoplastic IBD-affected colon. Cell 182, 672.e11–684.e11 (2020).

    Article  Google Scholar 

  11. Dziubańska-Kusibab, P. J., Berger, H., Battistini, F., Bouwman, B. A. M., Iftekhar, A., Katainen, R. et al. Colibactin DNA-damage signature indicates mutational impact in colorectal cancer. Nat. Med. 26, 1063–1069 (2020).

    Article  Google Scholar 

  12. Boot, A., Ng, A. W. T., Chong, F. T., Ho, S.-C., Yu, W., Tan, D. S. W. et al. Characterization of colibactin-associated mutational signature in an Asian oral squamous cell carcinoma and in other mucosal tumor types. Genome Res. 30, 803–813 (2020).

    Article  CAS  Google Scholar 

  13. Degasperi, A., Amarante, T. D., Czarnecki, J., Shooter, S., Zou, X., Glodzik, D. et al. A practical framework and online tool for mutational signature analyses show inter-tissue variation and driver dependencies. Nat. Cancer 1, 249–263 (2020).

    Article  Google Scholar 

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Acknowledgements

We thank H. Clevers and R. van Boxtel for critical reading of the manuscript.

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Author notes

  1. These authors contributed equally: Axel Rosendahl Huber, Cayetano Pleguezuelos-Manzano, Jens Puschhof

Authors and Affiliations

  1. The Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Axel Rosendahl Huber

  2. Oncode Institute, Hubrecht Institute, Utrecht, The Netherlands

    Axel Rosendahl Huber, Cayetano Pleguezuelos-Manzano & Jens Puschhof

  3. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, The Netherlands

    Cayetano Pleguezuelos-Manzano & Jens Puschhof

Authors
  1. Axel Rosendahl Huber
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  2. Cayetano Pleguezuelos-Manzano
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  3. Jens Puschhof
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Contributions

A.R.H., C.P.-M. and J.P. contributed equally to the conceptualisation, writing and editing of the manuscript. C.P.-M. generated the image illustration.

Corresponding authors

Correspondence to Axel Rosendahl Huber, Cayetano Pleguezuelos-Manzano or Jens Puschhof.

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Competing interests

The authors declare no competing interests.

Funding information

A.R.H., C.P.-M. and J.P. were supported by the Oncode Institute (partly financed by the Dutch Cancer Society). A.R.H. was supported by a VIDI grant from the NWO (no. 016.Vidi.171.023); C.P.-M. and J.P. were supported by the following grants: CRUK OPTIMISTICC (C10674/A27140), the Gravitation project CancerGenomiCs.nl, and the Netherlands Organ-on-Chip Initiative (024.003.001) from the Netherlands Organisation for Scientific Research (NWO) funded by the Ministry of Education, Culture and Science of the government of the Netherlands.

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Rosendahl Huber, A., Pleguezuelos-Manzano, C. & Puschhof, J. A bacterial mutational footprint in colorectal cancer genomes. Br J Cancer 124, 1751–1753 (2021). https://doi.org/10.1038/s41416-021-01273-5

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