Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis
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Título: | Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis |
Autor/a: | Petljak, Mia Alexandrov, Ludmil B. Brammeld, Jonathan S. Price, Stacey Wedge, David C. Grossmann, Sebastian Dawson, Kevin J. Ju, Young Seok Ioro, Francesco Castro Tubío, José Manuel Koh, Ching Chiek Georgakopoulos Soares, Ilias Rodríguez Martín, Bernardo Otlu, Burçak O'Meara, Sarah Butler, Adam P. Menzies, Andrew Bhosle, Shriram G. Raine, Keiran Jones, David R. Teague, Jon W. Beal, Kathryn Latimer, Calli O'Neill, Laura Zamora Berna, Jorge Aurelio Anderson, Elizabeth Patel, Nikita Maddison, Mark Ng, Bee Ling Graham, Jennifer Garnett, Mathew J. McDermott, Ultan Nik Zainal, Serena Campbell, Peter J. Stratton, Michael R. |
Centro/Departamento: | 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 |
Palabras chave: | Mutational signatures | Human cancer cell | Mutagenesis | APOBEC | |
Data: | 2019 |
Editor: | Elsevier |
Cita bibliográfica: | Petljak, M., Alexandrov, L., Brammeld, J., Price, S., Wedge, D., & Grossmann, S. et al. (2019). Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis. Cell, 176(6), 1282-1294.e20. doi: 10.1016/j.cell.2019.02.012 |
Resumo: | Multiple signatures of somatic mutations have beenidentified in cancer genomes. Exome sequences of1,001 human cancer cell lines and 577 xenograftsrevealed most common mutational signatures,indicating past activity of the underlying processes,usually in appropriate cancer types. To investigateongoing patterns of mutational-signature genera-tion, cell lines were cultured for extended periodsand subsequently DNA sequenced. Signatures ofdiscontinued exposures, including tobacco smokeand ultraviolet light, were not generatedin vitro. Sig-natures of normal and defective DNA repair and repli-cation continued to be generated at roughly stablemutation rates. Signatures of APOBEC cytidinedeaminase DNA-editing exhibited substantial fluctu-ations in mutation rate over time with episodic burstsof mutations. The initiating factors for the burstsare unclear, although retrotransposon mobilizationmay contribute. The examined cell lines constitutea resource of live experimental models of mutationalprocesses, which potentially retain patterns ofactivity and regulation operative in primary humancancers |
Versión do editor: | https://doi.org/10.1016/j.cell.2019.02.012 |
URI: | http://hdl.handle.net/10347/21301 |
DOI: | 10.1016/j.cell.2019.02.012 |
ISSN: | 0092-8674 |
E-ISSN: | 1097-4172 |
Dereitos: | Copyright © 2019 Published by Elsevier Inc. This work is under a Creative Commons Attribution 4.0 International (CC BY 4.0) |
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