The evolutionary landscape of colorectal tumorigenesis

Cross, William, Kovac, Michal, Mustonen, Ville, Temko, Daniel, Davis, Hayley, Baker, Ann-Marie, Biswas, Sujata, Arnold, Roland, Chegwidden, Laura, Gatenbee, Chandler, Anderson, Alexander R., Koelzer, Viktor H., Martinez, Pierre, Jiang, Xiaowei, Domingo, Enric, Woodcock, Dan J., Feng, Yun, Kovacova, Monika, Maughan, Tim, Jansen, Marnix, Rodriguez-Justo, Manuel, Ashraf, Shazad, Guy, Richard, Cunningham, Christopher, East, James E., Wedge, David C., Wang, Lai Mun, Palles, Claire, Heinimann, Karl, Sottoriva, Andrea, Leedham, Simon J., Graham, Trevor A., Tomlinson, Ian P. M., The S:CORT Consortium and Adams, Richard ORCID: https://orcid.org/0000-0003-3915-7243 2018. The evolutionary landscape of colorectal tumorigenesis. Nature Ecology and Evolution 2 (10) , pp. 1661-1672. 10.1038/s41559-018-0642-z

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Centre for Trials Research (CNTRR)
Additional Information:	R. Adams is a member of the S:CORT Consortium,
Publisher:	Nature Research (part of Springer Nature)
ISSN:	2397-334X
Date of Acceptance:	12 July 2018
Last Modified:	09 Nov 2022 10:54
URI:	https://orca.cardiff.ac.uk/id/eprint/141060

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