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

Nat Commun. 2020 Nov 9;11(1):5671. doi: 10.1038/s41467-020-19401-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Nitroquinoline-1-oxide / adverse effects
  • Animals
  • Cadherins / genetics
  • Carcinogenesis / chemically induced
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Disease Models, Animal
  • Disease Progression
  • Exome / genetics
  • Gene Expression Regulation, Neoplastic*
  • Genes, Neoplasm
  • Genes, p53 / genetics
  • Genomics*
  • Mice
  • Mice, Inbred C57BL
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Mutation
  • Neoplasm Invasiveness
  • Receptor, Notch1 / genetics


  • Cadherins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • fat1 protein, mouse
  • 4-Nitroquinoline-1-oxide