Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology.
Date
2020-11-09ICR Author
Author
Sequeira, I
Rashid, M
Tomás, IM
Williams, MJ
Graham, TA
Adams, DJ
Vigilante, A
Watt, FM
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
4-Nitroquinoline-1-oxide
Animals
Cadherins
Carcinogenesis
Carcinoma, Squamous Cell
Disease Models, Animal
Disease Progression
Exome
Gene Expression Regulation, Neoplastic
Genes, Neoplasm
Genes, p53
Genomics
Mice
Mice, Inbred C57BL
Mouth Neoplasms
Mutation
Neoplasm Invasiveness
Receptor, Notch1
Research team
Genomics & evolut dynam
Language
eng
Date accepted
2020-10-06
License start date
2020-11-09
Citation
Nature Communications, 2020, 11 (1), pp. 5671 -
Publisher
NATURE PORTFOLIO