Petljak, MiaAlexandrov, Ludmil B.Brammeld, Jonathan S.Price, StaceyWedge, David C.Grossmann, SebastianDawson, Kevin J.Ju, Young SeokIoro, FrancescoCastro Tubío, José ManuelKoh, Ching ChiekGeorgakopoulos Soares, IliasRodríguez Martín, BernardoOtlu, BurçakO'Meara, SarahButler, Adam P.Menzies, AndrewBhosle, Shriram G.Raine, KeiranJones, David R.Teague, Jon W.Beal, KathrynLatimer, CalliO'Neill, LauraZamora Berna, Jorge AurelioAnderson, ElizabethPatel, NikitaMaddison, MarkNg, Bee LingGraham, JenniferGarnett, Mathew J.McDermott, UltanNik Zainal, SerenaCampbell, Peter J.Stratton, Michael R.2020-04-102020-04-102019Petljak, 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.2019.02.0120092-8674http://hdl.handle.net/10347/21301Multiple 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 humancancersengCopyright © 2019 Published by Elsevier Inc. This work is under a Creative Commons Attribution 4.0 International (CC BY 4.0)https://creativecommons.org/licenses/by/4.0/Mutational signaturesHuman cancer cellMutagenesisAPOBECjournal article10.1016/j.cell.2019.02.0121097-4172open access