TY - JOUR
T1 - The evolutionary landscape of colorectal tumorigenesis
AU - Cross, William
AU - Kovac, Michal
AU - Mustonen, Ville
AU - Temko, Daniel
AU - Davis, Hayley
AU - Baker, Ann-Marie
AU - Biswas, Sujata
AU - Arnold, Roland
AU - Chegwidden, Laura
AU - Gatenbee, Chandler
AU - Anderson, Alexander R
AU - Koelzer, Viktor H
AU - Martinez, Pierre
AU - Jiang, Xiaowei
AU - Domingo, Enric
AU - Woodcock, Dan J
AU - Feng, Yun
AU - Kovacova, Monika
AU - Maughan, Tim
AU - Jansen, Marnix
AU - Rodriguez-Justo, Manuel
AU - Ashraf, Shazad
AU - Guy, Richard
AU - Cunningham, Christopher
AU - East, James E
AU - Wedge, David C
AU - Wang, Lai Mun
AU - Palles, Claire
AU - Heinimann, Karl
AU - Sottoriva, Andrea
AU - Leedham, Simon J
AU - Graham, Trevor A
AU - Tomlinson, Ian P M
AU - S:CORT Consortium
AU - Bach, Simon
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85053310111&partnerID=MN8TOARS
U2 - 10.1038/s41559-018-0642-z
DO - 10.1038/s41559-018-0642-z
M3 - Article
C2 - 30177804
VL - 2
SP - 1661
EP - 1672
JO - Nature Ecology and Evolution
JF - Nature Ecology and Evolution
IS - 10
ER -