Cross, W, Kovac, M, Mustonen, V et al. (53 more authors) (2018) The evolutionary landscape of colorectal tumorigenesis. Nature Ecology & Evolution, 2 (10). pp. 1661-1672. ISSN 2397-334X
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018, Springer Nature. This is an author produced version of a paper published in Nature Ecology & Evolution. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Clinical Cancer Research (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 30 Nov 2018 11:22 |
Last Modified: | 01 Mar 2019 01:39 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/s41559-018-0642-z |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:139375 |