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Publication : Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice.

First Author  Rose Li Y Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  394
PubMed ID  31959748 Mgi Jnum  J:286306
Mgi Id  MGI:6387456 Doi  10.1038/s41467-019-14261-4
Citation  Rose Li Y, et al. (2020) Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice. Nat Commun 11(1):394
abstractText  Ionising radiation (IR) is a recognised carcinogen responsible for cancer development in patients previously treated using radiotherapy, and in individuals exposed as a result of accidents at nuclear energy plants. However, the mutational signatures induced by distinct types and doses of radiation are unknown. Here, we analyse the genetic architecture of mammary tumours, lymphomas and sarcomas induced by high ((56)Fe-ions) or low (gamma) energy radiation in mice carrying Trp53 loss of function alleles. In mammary tumours, high-energy radiation is associated with induction of focal structural variants, leading to genomic instability and Met amplification. Gamma-radiation is linked to large-scale structural variants and a point mutation signature associated with oxidative stress. The genomic architecture of carcinomas, sarcomas and lymphomas arising in the same animals are significantly different. Our study illustrates the complex interactions between radiation quality, germline Trp53 deficiency and tissue/cell of origin in shaping the genomic landscape of IR-induced tumours.
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