Mutational signatures of ionizing radiation in second malignancies
| Autor: | Hayley J. Luxton, David Nicol, Chris Ogden, Tokhir Dadaev, Katalin Karaszi, Douglas F. Easton, David E. Neal, Michael R. Stratton, David C. Wedge, Adam Butler, William J. Howat, Jon W. Teague, Sam Behjati, Elizabeth Bancroft, Susanna L. Cooke, Yongwei Yu, Barbara Kremeyer, Peter Van Loo, Pardeep Kumar, Freddie C. Hamdy, Helen Davies, Gunes Gundem, Simon Tavaré, Sarah Thomas, Christopher S. Foster, Anthony C. H. Ng, Erik Mayer, Naomi Livni, Niedzica Camacho, Sarah O’Meara, Cyril Fisher, Gill Pelvender, Nening Dennis, Ultan McDermott, David T. Jones, Jorge Zamora, Adam Lambert, Andy G. Lynch, Mette Jorgensen, Manasa Ramakrishna, Bhavisha Khatri, Andy Menzies, Steven Hazell, Nimish Shah, Susan Merson, Jilur Ghori, Rosalind A. Eeles, Yong-Jie Lu, Anne Y. Warren, Claire Hardy, Adrienne M. Flanagan, Rebecca Shepherd, Tim Dudderidge, Jonathan Kay, Calli Latimer, Ludmil B. Alexandrov, G. Steven Bova, Patrick S. Tarpey, Serena Nik-Zainal, Claire Verrill, Hongwei Zhang, Steve Hawkins, P. Andrew Futreal, Christopher Greenman, Peter J. Campbell, Daniel Leongamornlert, Nischalan Pillay, Keiran Raine, Charlie E. Massi, Sandra L. Edwards, Alan J. Thompson, Lucy Matthews, Cathy Corbishley, Andrea L. Richardson, Adam Shlien, Lucy Stebbings, Christophe Badie, Hayley C. Whitaker, Nicola D. Roberts, Vincent J. Gnanapragasam, Zsofia Kote-Jarai, Daniel M. Berney, Colin Cooper, Daniel Brewer |
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| Přispěvatelé: | University of St Andrews. School of Medicine, University of St Andrews. Statistics, Nik-Zainal, Serena [0000-0001-5054-1727], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Chemistry(all) medicine.medical_treatment General Physics and Astronomy medicine.disease_cause Ionizing radiation Radiation Ionizing QD health care economics and organizations Genetics Osteosarcoma Mutation Multidisciplinary Manchester Cancer Research Centre Neoplasms Second Primary 3. Good health Female Science Breast Neoplasms Context (language use) QH426 Genetics Biology Physics and Astronomy(all) Article General Biochemistry Genetics and Molecular Biology RC0254 03 medical and health sciences Germline mutation SDG 3 - Good Health and Well-being medicine Humans QH426 Germ-Line Mutation Carcinogen Replication timing RC0254 Neoplasms. Tumors. Oncology (including Cancer) Biochemistry Genetics and Molecular Biology(all) ResearchInstitutes_Networks_Beacons/mcrc Prostatic Neoplasms Cancer DAS General Chemistry medicine.disease QD Chemistry Radiation therapy 030104 developmental biology Gene Deletion DNA Damage |
| Zdroj: | Europe PubMed Central Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-8 (2016) Behjati, S, Gundem, G, Wedge, DC, Roberts, ND, Tarpey, PS, Cooke, SL, Van, L P, Alexandrov, LB, Ramakrishna, M, Davies, H, Nik-Zainal, S, Hardy, C, Latimer, C, Raine, KM, Stebbings, L, Menzies, A, Jones, D, Shepherd, R, Butler, AP & Teague, JW 2016, ' Mutational signatures of ionizing radiation in second malignancies. ', Nature Communications, vol. 7 . https://doi.org/10.1038/ncomms12605 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms12605 |
| Popis: | 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. Ionizing radiation may induce irreparable DNA damage leading to cancer. Here, the authors identify a specific signature of mutations arising in patients exposed to ionizing radiation and suggest that radiation-induced tumorigenesis is associated with higher rates of genome-wide deletions and balanced inversions. |
| Databáze: | OpenAIRE |
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