dc.contributor.author | Cross, W | |
dc.contributor.author | Kovac, M | |
dc.contributor.author | Mustonen, V | |
dc.contributor.author | Temko, D | |
dc.contributor.author | Davis, H | |
dc.contributor.author | Baker, A-M | |
dc.contributor.author | Biswas, S | |
dc.contributor.author | Arnold, R | |
dc.contributor.author | Chegwidden, L | |
dc.contributor.author | Gatenbee, C | |
dc.contributor.author | Anderson, AR | |
dc.contributor.author | Koelzer, VH | |
dc.contributor.author | Martinez, P | |
dc.contributor.author | Jiang, X | |
dc.contributor.author | Domingo, E | |
dc.contributor.author | Woodcock, DJ | |
dc.contributor.author | Feng, Y | |
dc.contributor.author | Kovacova, M | |
dc.contributor.author | Maughan, T | |
dc.contributor.author | S:CORT Consortium, | |
dc.contributor.author | Jansen, M | |
dc.contributor.author | Rodriguez-Justo, M | |
dc.contributor.author | Ashraf, S | |
dc.contributor.author | Guy, R | |
dc.contributor.author | Cunningham, C | |
dc.contributor.author | East, JE | |
dc.contributor.author | Wedge, DC | |
dc.contributor.author | Wang, LM | |
dc.contributor.author | Palles, C | |
dc.contributor.author | Heinimann, K | |
dc.contributor.author | Sottoriva, A | |
dc.contributor.author | Leedham, SJ | |
dc.contributor.author | Graham, TA | |
dc.contributor.author | Tomlinson, IPM | |
dc.date.accessioned | 2018-09-06T10:04:44Z | |
dc.date.issued | 2018-10-01 | |
dc.identifier.citation | Nature ecology & evolution, 2018, 2 (10), pp. 1661 - 1672 | |
dc.identifier.issn | 2397-334X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2568 | |
dc.identifier.eissn | 2397-334X | |
dc.identifier.doi | 10.1038/s41559-018-0642-z | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 1661 - 1672 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | S:CORT Consortium | |
dc.subject | Humans | |
dc.subject | Adenoma | |
dc.subject | Carcinoma | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Evolution, Molecular | |
dc.subject | Mutation | |
dc.subject | Models, Biological | |
dc.subject | Carcinogenesis | |
dc.title | The evolutionary landscape of colorectal tumorigenesis. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-07-12 | |
rioxxterms.versionofrecord | 10.1038/s41559-018-0642-z | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature ecology & evolution | |
pubs.issue | 10 | |
pubs.notes | 6 months | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.volume | 2 | |
pubs.embargo.terms | 6 months | |
dc.contributor.icrauthor | Baker, Ann-Marie Clare | |
dc.contributor.icrauthor | Sottoriva, Andrea | |
dc.contributor.icrauthor | Graham, Trevor | |