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

Author

Listed:
  • Yun Rose Li

    (University of California San Francisco
    University of California San Francisco)

  • Kyle D. Halliwill

    (University of California San Francisco
    Abbvie)

  • Cassandra J. Adams

    (University of California San Francisco
    University of Oxford)

  • Vivek Iyer

    (Wellcome Trust Sanger Institute, Hinxton)

  • Laura Riva

    (Wellcome Trust Sanger Institute, Hinxton)

  • Rashid Mamunur

    (Wellcome Trust Sanger Institute, Hinxton)

  • Kuang-Yu Jen

    (University of California San Francisco
    University of California Davis Medical Center)

  • Reyno Rosario

    (University of California San Francisco)

  • Erik Fredlund

    (University of California San Francisco
    Doublestrand Bioinformatics)

  • Gillian Hirst

    (University of California San Francisco)

  • Ludmil B. Alexandrov

    (University of California, San Diego)

  • David Adams

    (Wellcome Trust Sanger Institute, Hinxton)

  • Allan Balmain

    (University of California San Francisco
    University of California San Francisco)

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.

Suggested Citation

  • Yun Rose Li & Kyle D. Halliwill & Cassandra J. Adams & Vivek Iyer & Laura Riva & Rashid Mamunur & Kuang-Yu Jen & Reyno Rosario & Erik Fredlund & Gillian Hirst & Ludmil B. Alexandrov & David Adams & Al, 2020. "Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14261-4
    DOI: 10.1038/s41467-019-14261-4
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