The evolutionary landscape of colorectal tumorigenesis
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 neoplas...
| প্রধান লেখক: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Springer Nature
2018
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| _version_ | 1826288698755383296 |
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| author | Cross, W Kovac, M Mustonen, V Temko, D Davis, H Baker, A Biswas, S Arnold, R Chegwidden, L Gatenbee, C Anderson, A Koelzer, V Martinez, P Jiang, X Domingo, E Woodcock, D Feng, Y Kovacova, M Maughan, T S:Cort Consortium Jansen, M Rodriguez-Justo, M Ashraf, S Guy, R Cunningham, C East, J Wedge, D Wang, L Palles, C Heinimann, K Sottoriva, A Leedham, S Graham, T Tomlinson, I |
| author_facet | Cross, W Kovac, M Mustonen, V Temko, D Davis, H Baker, A Biswas, S Arnold, R Chegwidden, L Gatenbee, C Anderson, A Koelzer, V Martinez, P Jiang, X Domingo, E Woodcock, D Feng, Y Kovacova, M Maughan, T S:Cort Consortium Jansen, M Rodriguez-Justo, M Ashraf, S Guy, R Cunningham, C East, J Wedge, D Wang, L Palles, C Heinimann, K Sottoriva, A Leedham, S Graham, T Tomlinson, I |
| author_sort | Cross, W |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:17:37Z |
| format | Journal article |
| id | oxford-uuid:a2ce9a44-8d14-4d13-9f21-a82192e1e16a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:17:37Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:a2ce9a44-8d14-4d13-9f21-a82192e1e16a2022-03-27T02:22:33ZThe evolutionary landscape of colorectal tumorigenesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a2ce9a44-8d14-4d13-9f21-a82192e1e16aEnglishSymplectic Elements at OxfordSpringer Nature2018Cross, WKovac, MMustonen, VTemko, DDavis, HBaker, ABiswas, SArnold, RChegwidden, LGatenbee, CAnderson, AKoelzer, VMartinez, PJiang, XDomingo, EWoodcock, DFeng, YKovacova, MMaughan, TS:Cort ConsortiumJansen, MRodriguez-Justo, MAshraf, SGuy, RCunningham, CEast, JWedge, DWang, LPalles, CHeinimann, KSottoriva, ALeedham, SGraham, TTomlinson, IThe 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. |
| spellingShingle | Cross, W Kovac, M Mustonen, V Temko, D Davis, H Baker, A Biswas, S Arnold, R Chegwidden, L Gatenbee, C Anderson, A Koelzer, V Martinez, P Jiang, X Domingo, E Woodcock, D Feng, Y Kovacova, M Maughan, T S:Cort Consortium Jansen, M Rodriguez-Justo, M Ashraf, S Guy, R Cunningham, C East, J Wedge, D Wang, L Palles, C Heinimann, K Sottoriva, A Leedham, S Graham, T Tomlinson, I The evolutionary landscape of colorectal tumorigenesis |
| title | The evolutionary landscape of colorectal tumorigenesis |
| title_full | The evolutionary landscape of colorectal tumorigenesis |
| title_fullStr | The evolutionary landscape of colorectal tumorigenesis |
| title_full_unstemmed | The evolutionary landscape of colorectal tumorigenesis |
| title_short | The evolutionary landscape of colorectal tumorigenesis |
| title_sort | evolutionary landscape of colorectal tumorigenesis |
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