Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology.
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Embargo End Date
ICR Authors
Authors
Sequeira, I
Rashid, M
Tomás, IM
Williams, MJ
Graham, TA
Adams, DJ
Vigilante, A
Watt, FM
Rashid, M
Tomás, IM
Williams, MJ
Graham, TA
Adams, DJ
Vigilante, A
Watt, FM
Document Type
Journal Article
Date
2020-11-09
Date Accepted
2020-10-06
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.
Citation
Nature Communications, 2020, 11 (1), pp. 5671 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Genomics & evolut dynam