The evolutionary landscape of colorectal tumorigenesis.

Cross, William and Kovac, Michal and Mustonen, Ville and Temko, Daniel and Davis, Hayley and Baker, Ann-Marie and Biswas, Sujata and Arnold, Roland and Chegwidden, Laura and Gatenbee, Chandler and Anderson, Alexander R and Koelzer, Viktor H and Martinez, Pierre and Jiang, Xiaowei and Domingo, Enric and Woodcock, Dan J and Feng, Yun and Kovacova, Monika and Maughan, Tim and Jansen, Marnix and Rodriguez-Justo, Manuel and Ashraf, Shazad and Guy, Richard and Cunningham, Christopher and East, James E and Wedge, David C and Wang, Lai Mun and Palles, Claire and Heinimann, Karl and Sottoriva, Andrea and Leedham, Simon J and 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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