Tools
Tools
Behjati, Sam, Gundem, Gunes, Wedge, David C., Roberts, Nicola D., Tarpey, Patrick S., Cooke, Susanna L., Van Loo, Peter, Alexandrov, Ludmil B., Ramakrishna, Manasa, Davies, Helen, Nik-Zainal, Serena, Hardy, Claire, Latimer, Calli, Raine, Keiran M., Stebbings, Lucy, Menzies, Andy, Jones, David, Shepherd, Rebecca, Butler, Adam P., Teague, Jon W., Jorgensen, Mette, Khatri, Bhavisha, Pillay, Nischalan, Shlien, Adam, Futreal, P. Andrew, Badie, Christophe, Cooper, Colin S. 
ORCID: https://orcid.org/0000-0003-2013-8042, Eeles, Rosalind A., Easton, Douglas, Foster, Christopher, Neal, David E., Brewer, Daniel S. ORCID: https://orcid.org/0000-0003-4753-9794, Hamdy, Freddie, Lu, Yong-Jie, Lynch, Andrew G., Massi, Charlie E., Ng, Anthony, Whitaker, Hayley C., Yu, Yongwei, Zhang, Hongwei, Bancroft, Elizabeth, Berney, Dan, Camacho, Niedzica, Corbishley, Cathy, Dadaev, Tokhir, Dennis, Nening, Dudderidge, Tim, Edwards, Sandra, Fisher, Cyril, Ghori, Jilur, Gnanapragasam, Vincent J., Greenman, Christopher, Hawkins, Steve, Hazell, Steven, Howat, Will, Karaszi, Katalin, Kay, Jonathan, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel, Livni, Naomi, Luxton, Hayley, Matthews, Lucy, Mayer, Erik, Merson, Susan, Nicol, David, Ogden, Christopher, O'Meara, Sarah, Pelvender, Gill, Shah, Nimish C., Tavare, Simon, Thomas, Sarah, Thompson, Alan, Verrill, Claire, Warren, Anne, Zamora, Jorge, McDermott, Ultan, Bova, G. Steven, Richardson, Andrea L., Flanagan, Adrienne M., Stratton, Michael R. and Campbell, Peter J.
(2016)
Mutational signatures of ionizing radiation in second malignancies.
Nature Communications, 7.
ISSN 2041-1723
Preview |
PDF (Published manuscript)
- Published Version
Download (1MB) | Preview |
Abstract
Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1–100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential.
| Item Type: | Article |
|---|---|
| Additional Information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Uncontrolled Keywords: | sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Computing Sciences Faculty of Science > School of Natural Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Science > Research Groups > Computational Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | Pure Connector |
| Date Deposited: | 26 Sep 2016 10:00 |
| Last Modified: | 19 Oct 2023 01:47 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/60579 |
| DOI: | 10.1038/ncomms12605 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |