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dc.contributor.authorBehjati, S
dc.contributor.authorGundem, G
dc.contributor.authorWedge, DC
dc.contributor.authorRoberts, ND
dc.contributor.authorTarpey, PS
dc.contributor.authorCooke, SL
dc.contributor.authorVan Loo, P
dc.contributor.authorAlexandrov, LB
dc.contributor.authorRamakrishna, M
dc.contributor.authorDavies, H
dc.contributor.authorNik-Zainal, S
dc.contributor.authorHardy, C
dc.contributor.authorLatimer, C
dc.contributor.authorRaine, KM
dc.contributor.authorStebbings, L
dc.contributor.authorMenzies, A
dc.contributor.authorJones, D
dc.contributor.authorShepherd, R
dc.contributor.authorButler, AP
dc.contributor.authorTeague, JW
dc.contributor.authorJorgensen, M
dc.contributor.authorKhatri, B
dc.contributor.authorPillay, N
dc.contributor.authorShlien, A
dc.contributor.authorFutreal, PA
dc.contributor.authorBadie, C
dc.contributor.authorICGC Prostate Group
dc.contributor.authorMcDermott, U
dc.contributor.authorBova, GS
dc.contributor.authorRichardson, AL
dc.contributor.authorFlanagan, AM
dc.contributor.authorStratton, MR
dc.contributor.authorCampbell, PJ
dc.date.accessioned2018-10-18T11:20:56Z
dc.date.issued2016-09-12
dc.identifier.citationNature communications, 2016, 7 pp. 12605 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2903
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms12605
dc.description.abstractIonizing 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.
dc.formatElectronic
dc.format.extent12605 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectICGC Prostate Group
dc.subjectHumans
dc.subjectOsteosarcoma
dc.subjectBreast Neoplasms
dc.subjectProstatic Neoplasms
dc.subjectNeoplasms, Second Primary
dc.subjectDNA Damage
dc.subjectGene Deletion
dc.subjectMutation
dc.subjectGerm-Line Mutation
dc.subjectRadiation, Ionizing
dc.subjectFemale
dc.subjectMale
dc.titleMutational signatures of ionizing radiation in second malignancies.
dc.typeJournal Article
dcterms.dateAccepted2016-07-13
rioxxterms.versionofrecord10.1038/ncomms12605
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-09-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume7
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden
dc.contributor.icrauthorFisher, Cyrilen
dc.contributor.icrauthorKote-Jarai, Zsofiaen
dc.contributor.icrauthorKumar, Pardeepen


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