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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; et al (2018). The evolutionary landscape of colorectal tumorigenesis. Nature Ecology and Evolution, 2(10):1661-1672.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2018
Deposited On:26 Sep 2019 13:38
Last Modified:10 Nov 2019 07:02
Publisher:Nature Publishing Group
ISSN:2397-334X
OA Status:Green
Publisher DOI:https://doi.org/10.1038/s41559-018-0642-z
PubMed ID:30177804

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