The evolutionary landscape of colorectal tumorigenesis
| Autor: | 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., Adams, R., Bach, S., Beggs, A., Brown, L., Buffa, F., Cazier, J.-B., Blake, A., Wu, C.-H., Chatzpili, E., Richman, S., Dunne, P., Harkin, P., Higgins, G., Hill, J., Holmes, C., Horgan, D., Kaplan, R., Kennedy, R., Lawler, M., Leedham, S., McDermott, U., McKenna, G., Middleton, G., Morton, D., Murray, G., Quirke, P., Salto-Tellez, M., Samuel, L., Schuh, A., Sebag-Montefiore, D., Seymour, M., Sharma, R., Sullivan, R., Tomlinson, I., West, N., Wilson, R., Jansen, M., Rodriguez-Justo, M., Ashraf, S., Guy, R., Cunningham, C., East, J.E., Wedge, D.C., Wang, L.M., Palles, C., Heinimann, K., Sottoriva, A., Graham, T.A., Tomlinson, I.P.M. |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adenoma Fitness landscape Carcinogenesis Evolutionary landscape Biology medicine.disease_cause Models Biological Article Evolution Molecular 03 medical and health sciences medicine Humans Stabilizing selection Ecology Evolution Behavior and Systematics Exome sequencing Ecology Manchester Cancer Research Centre Genetic heterogeneity ResearchInstitutes_Networks_Beacons/mcrc Carcinoma Cancer medicine.disease 030104 developmental biology Evolutionary biology Mutation Colorectal Neoplasms |
| Zdroj: | 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, Adams, R, Bach, S, Beggs, A, Brown, L, Buffa, F, Cazier, J-B, Domingo, E, Blake, A, Wu, C-H, Chatzpili, E, Richman, S, Dunne, P, Harkin, P, Higgins, G, Hill, J, Holmes, C, Horgan, D, Kaplan, R, Kennedy, R, Lawler, M, Leedham, S, Maughan, T, McDermott, U, McKenna, G, Middleton, G, Morton, D, Murray, G, Quirke, P, Salto-Tellez, M, Samuel, L, Schuh, A, Sebag-Montefiore, D, Seymour, M, Sharma, R, Sullivan, R, Tomlinson, I, West, N, Wilson, R, Jansen, M, Rodriguez-Justo, M, Ashraf, S, Guy, R, Cunningham, C, East, J E, Wedge, D C, Wang, L M, Palles, C, Heinimann, K, Sottoriva, A, Leedham, S, Graham, T A & Tomlinson, I P M 2018, ' The evolutionary landscape of colorectal tumorigenesis ', Nature Ecology and Evolution . https://doi.org/10.1038/s41559-018-0642-z Nature ecology & evolution |
| ISSN: | 2397-334X |
| DOI: | 10.1038/s41559-018-0642-z |
| Popis: | The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome/exome sequencing of 24 benign and malignant colorectal tumours, we probe the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations, which are 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 stabilising selection. |
| Databáze: | OpenAIRE |
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