RT Journal Article
T1 Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis
A1 Petljak, Mia
A1 Alexandrov, Ludmil B.
A1 Brammeld, Jonathan S.
A1 Price, Stacey
A1 Wedge, David C.
A1 Grossmann, Sebastian
A1 Dawson, Kevin J.
A1 Ju, Young Seok
A1 Ioro, Francesco
A1 Castro Tubío, José Manuel
A1 Koh, Ching Chiek
A1 Georgakopoulos Soares, Ilias
A1 Rodríguez Martín, Bernardo
A1 Otlu, Burçak
A1 O'Meara, Sarah
A1 Butler, Adam P.
A1 Menzies, Andrew
A1 Bhosle, Shriram G.
A1 Raine, Keiran
A1 Jones, David R.
A1 Teague, Jon W.
A1 Beal, Kathryn
A1 Latimer, Calli
A1 O'Neill, Laura
A1 Zamora Berna, Jorge Aurelio
A1 Anderson, Elizabeth
A1 Patel, Nikita
A1 Maddison, Mark
A1 Ng, Bee Ling
A1 Graham, Jennifer
A1 Garnett, Mathew J.
A1 McDermott, Ultan
A1 Nik Zainal, Serena
A1 Campbell, Peter J.
A1 Stratton, Michael R.
K1 Mutational signatures
K1 Human cancer cell
K1 Mutagenesis
K1 APOBEC
AB 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
PB Elsevier
SN 0092-8674
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21301
UL http://hdl.handle.net/10347/21301
LA eng
NO 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
NO This work was supported by Wellcome grants 098051 and 206194; CancerResearch UK Grand Challenge Award C98/A24032 to L.B.A. and B.O.; the LiKa Shing Foundation and National Institute for Health Research Oxford Biomedical Research Centre to D.C.W.; ED481A-2016/151 from Xunta de Galicia to B.R.–M.
DS Minerva
RD 24 abr 2026