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The evolutionary landscape of colorectal tumorigenesis

Cross, W; Kovac, M; Mustonen, V; Temko, D; Davis, H; Baker, A-M; Biswas, S; ... Tomlinson, IPM; + view all (2018) The evolutionary landscape of colorectal tumorigenesis. Nature Ecology & Evolution , 2 (10) pp. 1661-1672. 10.1038/s41559-018-0642-z. Green open access

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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.

Type: Article
Title: The evolutionary landscape of colorectal tumorigenesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41559-018-0642-z
Publisher version: https://doi.org/10.1038/s41559-018-0642-z
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Ecology, Evolutionary Biology, Environmental Sciences & Ecology, ESOPHAGEAL ADENOCARCINOMA, SEQUENCING PROVIDES, BARRETTS-ESOPHAGUS, TUMOR EVOLUTION, CANCER, GENOME, APC, HETEROGENEITY, MUTATIONS, CARCINOMA
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > UCL SLASH
UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities
UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities > Arts and Sciences (BASc)
URI: https://discovery.ucl.ac.uk/id/eprint/10073156
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