The evolutionary landscape of colorectal tumorigenesis

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

doi:10.1038/s41559-018-0642-z

The evolutionary landscape of colorectal tumorigenesis

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

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	1661-1672
Number of pages	12
Journal	Nature Ecology & Evolution
Volume	2
Issue number	10
DOIs	https://doi.org/10.1038/s41559-018-0642-z
Publication status	Published - 31 Aug 2018

Keywords / Materials (for Non-textual outputs)

Adenoma/genetics
Carcinogenesis/genetics
Carcinoma/genetics
Colorectal Neoplasms/genetics
Evolution, Molecular
Humans
Models, Biological
Mutation

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10.1038/s41559-018-0642-z

http://eprints.whiterose.ac.uk/139375/

Cite this

Cross, W., Kovac, M., Mustonen, V., Temko, D., Davis, H., Baker, A.-M., Biswas, S., Arnold, R., Chegwidden, L., Gatenbee, C., Anderson, A. R., Koelzer, V. H., Martinez, P., Jiang, X., Domingo, E., Woodcock, D. J., Feng, Y., Kovacova, M., Maughan, T., ... Tomlinson, I. P. M. (2018). The evolutionary landscape of colorectal tumorigenesis. Nature Ecology & Evolution, 2(10), 1661-1672. https://doi.org/10.1038/s41559-018-0642-z

@article{171a3474800d4fcbaed5ccd56a736688,

title = "The evolutionary landscape of colorectal tumorigenesis",

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 {\textquoteleft}punctuated{\textquoteright} fashion. We conclude that adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilizing selection.",

keywords = "Adenoma/genetics, Carcinogenesis/genetics, Carcinoma/genetics, Colorectal Neoplasms/genetics, Evolution, Molecular, Humans, Models, Biological, Mutation",

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

year = "2018",

month = aug,

day = "31",

doi = "10.1038/s41559-018-0642-z",

language = "English",

volume = "2",

pages = "1661--1672",

journal = "Nature Ecology & Evolution",

issn = "2397-334X",

publisher = "Nature Publishing Group",

number = "10",

}

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 2018, 'The evolutionary landscape of colorectal tumorigenesis', Nature Ecology & Evolution, vol. 2, no. 10, pp. 1661-1672. https://doi.org/10.1038/s41559-018-0642-z

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 - S:CORT Consortium

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

PY - 2018/8/31

Y1 - 2018/8/31

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.

KW - Adenoma/genetics

KW - Carcinogenesis/genetics

KW - Carcinoma/genetics

KW - Colorectal Neoplasms/genetics

KW - Evolution, Molecular

KW - Humans

KW - Models, Biological

KW - Mutation

U2 - 10.1038/s41559-018-0642-z

DO - 10.1038/s41559-018-0642-z

M3 - Article

C2 - 30177804

SN - 2397-334X

VL - 2

SP - 1661

EP - 1672

JO - Nature Ecology & Evolution

JF - Nature Ecology & Evolution

IS - 10

ER -

The evolutionary landscape of colorectal tumorigenesis

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Keywords / Materials (for Non-textual outputs)

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