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, Fiona M Watt

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)
101 Downloads (Pure)


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 p53Notch1 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.

Original languageEnglish
Article number5671
Number of pages13
JournalNature Communications
Issue number1
Early online date9 Nov 2020
Publication statusPublished - Dec 2020


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


Dive into the research topics of 'Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology'. Together they form a unique fingerprint.

Cite this