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

First Author  Sequeira I Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  5671
PubMed ID  33168804 Mgi Jnum  J:301008
Mgi Id  MGI:6504414 Doi  10.1038/s41467-020-19401-9
Citation  Sequeira I, et al. (2020) Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology. Nat Commun 11(1):5671
abstractText  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-alpha3 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.
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