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 and Tomlinson, Ian P M (2018) The evolutionary landscape of colorectal tumorigenesis. Nature ecology & evolution, 2 (10). pp. 1661-1672. ISSN 2397-334X.

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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
Subjects: QZ Pathology. Oncology
WO Surgery
Divisions: Clinical Support > Pathology
Planned IP Care > General Surgery
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Depositing User: Mrs Semanti Chakraborty
Date Deposited: 21 Jun 2019 15:23
Last Modified: 21 Jun 2019 15:23

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