Nature communications, 2020-01, Vol.11 (1), p.394-15, Article 394
2020
Details
- Autor(en) / Beteiligte
- Titel
- Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice
- Ist Teil von
- Nature communications, 2020-01, Vol.11 (1), p.394-15, Article 394
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Alma/SFX Local Collection
- Beschreibungen/Notizen
- 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 ( 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-14261-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_adf081533e9d46c2b04cbf253b8a5fd4
- Format
- –
- Schlagworte
- Accidents, Animals, Architecture, Cancer, Carcinogenesis - genetics, Carcinogenesis - radiation effects, Carcinogens, Carcinoma, DNA Damage - radiation effects, DNA Mutational Analysis, Dose-Response Relationship, Radiation, Female, Gamma rays, Gene Amplification - radiation effects, Genetic analysis, Genomic instability, Genomic Instability - radiation effects, Germ-Line Mutation, Humans, Ionizing radiation, Iron isotopes, Lymphoma, Male, Mice, Mice, Knockout, Mutants, Mutation, Neoplasms, Radiation-Induced - genetics, Neoplasms, Radiation-Induced - pathology, Nuclear accidents & safety, Nuclear energy, Nuclear engineering, Nuclear reactors, Oxidative stress, p53 Protein, Point mutation, Point Mutation - radiation effects, Proto-Oncogene Proteins c-met - genetics, Radiation Injuries, Experimental - genetics, Radiation Injuries, Experimental - pathology, Radiation therapy, Science & Technology - Other Topics, Signatures, Tumor Suppressor Protein p53 - genetics, Tumors, Whole Genome Sequencing