Mutational signatures of ionizing radiation in second malignancies
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Author
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.
Eeles, Rosalind A.
Easton, Douglas
Foster, Christopher
Neal, David E.
Brewer, Daniel S.
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.
Campbell, Peter J.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncomms12605Metadata
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Behjati, S., G. Gundem, D. C. Wedge, N. D. Roberts, P. S. Tarpey, S. L. Cooke, P. Van Loo, et al. 2016. “Mutational signatures of ionizing radiation in second malignancies.” Nature Communications 7 (1): 12605. doi:10.1038/ncomms12605. http://dx.doi.org/10.1038/ncomms12605.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027243/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407602
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