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

Inês Sequeira, Mamunur Rashid, Inês M. Tomás, Marc J. Williams, Trevor A. Graham, David J. Adams, Alessandra Vigilante and Fiona M. Watt ()
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Inês Sequeira: King’s College London, Guy’s Hospital, Great Maze Pond
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

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19401-9

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