Mutational signatures of ionizing radiation in second malignancies
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.
Citation
Behjati , S , Gundem , G , Wedge , D C , Roberts , N D , Tarpey , P S , Cooke , S L , Van Loo , P , Alexandrov , L B , Ramakrishna , M , Davies , H , Nik-Zainal , S , Hardy , C , Latimer , C , Raine , K M , Stebbings , L , Menzies , A , Jones , D , Shepherd , R , Butler , A P , Teague , J W , Jorgensen , M , Khatri , B , Pillay , N , Shlien , A , Futreal , P A , Badie , C , McDermott , U , Bova , G S , Richardson , A L , Flanagan , A M , Stratton , M R , Campbell , P J & ICGC Prostate Group 2016 , ' Mutational signatures of ionizing radiation in second malignancies ' , Nature Communications , vol. 7 , 12605 . https://doi.org/10.1038/ncomms12605
Publication
Nature Communications
Status
Peer reviewed
ISSN
2041-1723Type
Journal article
Rights
© The Author(s) 2016. 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/
Description
Sequencing data have been deposited at the European Genome-Phenome Archive (EGA, http://www.ebi.ac.uk/ega/), which is hosted by the European Bioinformatics Institute; accession numbers EGAS00001000138; EGAS00001000147; EGAS00001000195.Collections
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