The evolutionary landscape of colorectal tumorigenesis.
Loading...
Embargo End Date
ICR Authors
Authors
Cross, W
Kovac, M
Mustonen, V
Temko, D
Davis, H
Baker, A-M
Biswas, S
Arnold, R
Chegwidden, L
Gatenbee, C
Anderson, AR
Koelzer, VH
Martinez, P
Jiang, X
Domingo, E
Woodcock, DJ
Feng, Y
Kovacova, M
Maughan, T
S:CORT Consortium,
Jansen, M
Rodriguez-Justo, M
Ashraf, S
Guy, R
Cunningham, C
East, JE
Wedge, DC
Wang, LM
Palles, C
Heinimann, K
Sottoriva, A
Leedham, SJ
Graham, TA
Tomlinson, IPM
Kovac, M
Mustonen, V
Temko, D
Davis, H
Baker, A-M
Biswas, S
Arnold, R
Chegwidden, L
Gatenbee, C
Anderson, AR
Koelzer, VH
Martinez, P
Jiang, X
Domingo, E
Woodcock, DJ
Feng, Y
Kovacova, M
Maughan, T
S:CORT Consortium,
Jansen, M
Rodriguez-Justo, M
Ashraf, S
Guy, R
Cunningham, C
East, JE
Wedge, DC
Wang, LM
Palles, C
Heinimann, K
Sottoriva, A
Leedham, SJ
Graham, TA
Tomlinson, IPM
Document Type
Journal Article
Date
2018-10-01
Date Accepted
2018-07-12
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.
Citation
Nature ecology & evolution, 2018, 2 (10), pp. 1661 - 1672
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2397-334X
eISSN
2397-334X