Mutational signatures of ionizing radiation in second malignancies
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 mali...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2016
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| _version_ | 1797070560617824256 |
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| author | Behjati, S Gundem, G Wedge, DC Roberts, ND Tarpey, PS Cooke, SL Van Loo, 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 Jorgensen, M Khatri, B Pillay, N Shlien, A Futreal, PA Badie, C McDermott, U Bova, GS Richardson, AL Flanagan, AM Stratton, MR Campbell, PJ |
| author_facet | Behjati, S Gundem, G Wedge, DC Roberts, ND Tarpey, PS Cooke, SL Van Loo, 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 Jorgensen, M Khatri, B Pillay, N Shlien, A Futreal, PA Badie, C McDermott, U Bova, GS Richardson, AL Flanagan, AM Stratton, MR Campbell, PJ |
| author_sort | Behjati, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:40:37Z |
| format | Journal article |
| id | oxford-uuid:5b69a5d4-689f-4fc2-b01d-f4df98140415 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:40:37Z |
| publishDate | 2016 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:5b69a5d4-689f-4fc2-b01d-f4df981404152022-03-26T17:22:06ZMutational signatures of ionizing radiation in second malignanciesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5b69a5d4-689f-4fc2-b01d-f4df98140415EnglishSymplectic Elements at OxfordSpringer Nature2016Behjati, SGundem, GWedge, DCRoberts, NDTarpey, PSCooke, SLVan Loo, PAlexandrov, LBRamakrishna, MDavies, HNik-Zainal, SHardy, CLatimer, CRaine, KMStebbings, LMenzies, AJones, DShepherd, RButler, APTeague, JWJorgensen, MKhatri, BPillay, NShlien, AFutreal, PABadie, CMcDermott, UBova, GSRichardson, ALFlanagan, AMStratton, MRCampbell, PJIonizing 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. |
| spellingShingle | Behjati, S Gundem, G Wedge, DC Roberts, ND Tarpey, PS Cooke, SL Van Loo, 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 Jorgensen, M Khatri, B Pillay, N Shlien, A Futreal, PA Badie, C McDermott, U Bova, GS Richardson, AL Flanagan, AM Stratton, MR Campbell, PJ Mutational signatures of ionizing radiation in second malignancies |
| title | Mutational signatures of ionizing radiation in second malignancies |
| title_full | Mutational signatures of ionizing radiation in second malignancies |
| title_fullStr | Mutational signatures of ionizing radiation in second malignancies |
| title_full_unstemmed | Mutational signatures of ionizing radiation in second malignancies |
| title_short | Mutational signatures of ionizing radiation in second malignancies |
| title_sort | mutational signatures of ionizing radiation in second malignancies |
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