Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis
| Autor: | David C. Wedge, Michael R. Stratton, Kevin J. Dawson, Sebastian Grossmann, Peter J. Campbell, Jonathan S. Brammeld, Ilias Georgakopoulos-Soares, Young Seok Ju, Sarah O’Meara, Keiran Raine, Calli Latimer, Francesco Iorio, Bee Ling Ng, Burcak Otlu, Kathryn Beal, Jorge Zamora, Adam Butler, Shriram G. Bhosle, Bernardo Rodriguez-Martin, Jennifer Graham, Jon W. Teague, Mark Maddison, Elizabeth Anderson, Nikita Patel, Ludmil B. Alexandrov, Ultan McDermott, Mathew J. Garnett, David Jones, Ching Chiek Koh, Andrew Menzies, Stacey Price, Laura O’Neill, Serena Nik-Zainal, Mia Petljak, Jose M. C. Tubio |
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| Přispěvatelé: | Nik-Zainal Abidin, Serena [0000-0001-5054-1727], Apollo - University of Cambridge Repository, Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Zooloxía, Xenética e Antropoloxía Física |
| Rok vydání: | 2019 |
| Předmět: |
APOBEC
Mutation rate DNA Copy Number Variations Mutational signatures Somatic hypermutation mutational signatures Biology Article General Biochemistry Genetics and Molecular Biology episodic mutagenesis 03 medical and health sciences 0302 clinical medicine APOBEC Deaminases Ultraviolet light Humans Exome Proteogenomics 030304 developmental biology Genetics Human cancer cell 0303 health sciences cancer cell lines Manchester Cancer Research Centre ResearchInstitutes_Networks_Beacons/mcrc Mutagenesis APOBEC deaminases Cytidine deaminase Thoracic Neoplasms 3. Good health xenografts Mutation 030217 neurology & neurosurgery |
| Zdroj: | Cell Petljak, M, Alexandrov, L B, Brammeld, J S, Price, S, Wedge, D C, Grossmann, S, Dawson, K J, Ju, Y S, Iorio, F, Tubio, J M C, Koh, C C, Georgakopoulos-Soares, I, Rodríguez-Martín, B, Otlu, B, O'Meara, S, Butler, A P, Menzies, A, Bhosle, S G, Raine, K, Jones, D R, Teague, J W, Beal, K, Latimer, C, O'Neill, L, Zamora, J, Anderson, E, Patel, N, Maddison, M, Ng, B L, Graham, J, Garnett, M J, McDermott, U, Nik-Zainal, S, Campbell, P J & Stratton, M R 2019, ' Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis ', Cell . https://doi.org/10.1016/j.cell.2019.02.012 Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname |
| DOI: | 10.1016/j.cell.2019.02.012 |
| Popis: | Summary Multiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced. Signatures of discontinued exposures, including tobacco smoke and ultraviolet light, were not generated in vitro. Signatures of normal and defective DNA repair and replication continued to be generated at roughly stable mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing exhibited substantial fluctuations in mutation rate over time with episodic bursts of mutations. The initiating factors for the bursts are unclear, although retrotransposon mobilization may contribute. The examined cell lines constitute a resource of live experimental models of mutational processes, which potentially retain patterns of activity and regulation operative in primary human cancers. Graphical Abstract Highlights • Annotation of mutational signatures across 1,001 cancer cell lines and 577 PDXs • Activities of mutational processes determined over time in cancer cell lines • APOBEC-associated mutagenesis is often ongoing and can be episodic • Detection of mutational signatures by single-cell sequencing An analysis of 1,001 human cancer cell lines and 577 xenografts shows that mutagenesis associated with the cytodine deaminase APOBEC occurs in episodic bursts in contrast to mutation signatures associated with DNA replication and repair. |
| Databáze: | OpenAIRE |
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