Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice.
Nat Commun
; 11(1): 394, 2020 01 20.
Article
em En
| MEDLINE
| ID: mdl-31959748
ABSTRACT
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 (56Fe-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Lesões Experimentais por Radiação
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Proteína Supressora de Tumor p53
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Instabilidade Genômica
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Carcinogênese
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Neoplasias Induzidas por Radiação
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos