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Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology

Author

Listed:
  • Inês Sequeira

    (King’s College London, Guy’s Hospital, Great Maze Pond
    Queen Mary University of London)

  • Mamunur Rashid

    (The Wellcome Trust Sanger Institute)

  • Inês M. Tomás

    (King’s College London, Guy’s Hospital, Great Maze Pond)

  • Marc J. Williams

    (Barts Cancer Institute, Queen Mary University of London)

  • Trevor A. Graham

    (Barts Cancer Institute, Queen Mary University of London)

  • David J. Adams

    (The Wellcome Trust Sanger Institute)

  • Alessandra Vigilante

    (King’s College London, Guy’s Hospital, Great Maze Pond)

  • Fiona M. Watt

    (King’s College London, Guy’s Hospital, Great Maze Pond)

Abstract

To establish whether 4-nitroquinoline N-oxide-induced carcinogenesis mirrors the heterogeneity of human oral squamous cell carcinoma (OSCC), we have performed genomic analysis of mouse tongue lesions. The mutational signatures of human and mouse OSCC overlap extensively. Mutational burden is higher in moderate dysplasias and invasive SCCs than in hyperplasias and mild dysplasias, although mutations in p53, Notch1 and Fat1 occur in early lesions. Laminin-α3 mutations are associated with tumour invasiveness and Notch1 mutant tumours have an increased immune infiltrate. Computational modelling of clonal dynamics indicates that high genetic heterogeneity may be a feature of those mild dysplasias that are likely to progress to more aggressive tumours. These studies provide a foundation for exploring OSCC evolution, heterogeneity and progression.

Suggested Citation

  • Inês Sequeira & Mamunur Rashid & Inês M. Tomás & Marc J. Williams & Trevor A. Graham & David J. Adams & Alessandra Vigilante & Fiona M. Watt, 2020. "Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19401-9
    DOI: 10.1038/s41467-020-19401-9
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    Cited by:

    1. Robert Saddawi-Konefka & Aoife O’Farrell & Farhoud Faraji & Lauren Clubb & Michael M. Allevato & Shawn M. Jensen & Bryan S. Yung & Zhiyong Wang & Victoria H. Wu & Nana-Ama Anang & Riyam Al Msari & Shi, 2022. "Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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