Mutational signatures of ionizing radiation in second malignancies

Sam Behjati, Gunes Gundem, David C. Wedge, Nicola D. Roberts, Patrick S. Tarpey, Susanna L. Cooke, Peter Van Loo, Ludmil B. Alexandrov, Manasa Ramakrishna, Helen Davies, Serena Nik-Zainal, Claire Hardy, Calli Latimer, Keiran M. Raine, Lucy Stebbings, Andy Menzies, David Jones, Rebecca Shepherd, Adam P. Butler, Jon W. TeagueMette Jorgensen, Bhavisha Khatri, Nischalan Pillay, Adam Shlien, P. Andrew Futreal, Christophe Badie, Ultan McDermott, G. Steven Bova, Andrea L. Richardson, Adrienne M. Flanagan, Michael R. Stratton, Peter J. Campbell*, ICGC Prostate Group

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

183 Citations (Scopus)
3 Downloads (Pure)


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.

Original languageEnglish
Article number12605
Number of pages8
JournalNature Communications
Publication statusPublished - 12 Sept 2016


Dive into the research topics of 'Mutational signatures of ionizing radiation in second malignancies'. Together they form a unique fingerprint.

Cite this