Journal article
The evolutionary landscape of colorectal tumorigenesis
- Abstract:
- The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, we investigate the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations—considered to be functionally important in the carcinogenic process—that have not swept to fixation, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas by widespread aneusomies that are usually clonal and often accrue in a ‘punctuated’ fashion. We conclude that adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilizing selection.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 87.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41559-018-0642-z
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Ecology and Evolution More from this journal
- Volume:
- 2
- Pages:
- 1661–1672
- Publication date:
- 2018-08-31
- Acceptance date:
- 2018-07-12
- DOI:
- ISSN:
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2397-334X
- Pmid:
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30177804
- Language:
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English
- Keywords:
- Pubs id:
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pubs:914597
- UUID:
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uuid:a2ce9a44-8d14-4d13-9f21-a82192e1e16a
- Local pid:
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pubs:914597
- Source identifiers:
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914597
- Deposit date:
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2018-09-14
- ARK identifier:
Terms of use
- Copyright holder:
- Cross et al
- Copyright date:
- 2018
- Notes:
- This is the accepted manuscript version of the article. The final version is available online from Springer Nature at: https://doi.org/10.1038/s41559-018-0642-z
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