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

Rose Li Y., Halliwill KD., Adams CJ., Iyer V., Riva L., Mamunur R., Jen K-Y., del Rosario R., Fredlund E., Hirst G., Alexandrov LB., Adams D., Balmain A.

<jats:title>Abstract</jats:title><jats:p>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 (<jats:sup>56</jats:sup>Fe-ions) or low (gamma) energy radiation in mice carrying <jats:italic>Trp53</jats:italic> loss of function alleles. In mammary tumours, high-energy radiation is associated with induction of focal structural variants, leading to genomic instability and <jats:italic>Met</jats:italic> 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 <jats:italic>Trp53</jats:italic> deficiency and tissue/cell of origin in shaping the genomic landscape of IR-induced tumours.</jats:p>

DOI

10.1038/s41467-019-14261-4

Type

Journal article

Journal

Nature Communications

Publisher

Springer Science and Business Media LLC

Publication Date

12/2020

Volume

11

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