Details

Autor(en) / Beteiligte

• Sequeira, Inês
• Rashid, Mamunur
• Tomás, Inês M.
• Williams, Marc J.
• Graham, Trevor A.
• Adams, David J.
• Vigilante, Alessandra
• Watt, Fiona M.

Titel

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

Ist Teil von

• Nature communications, 2020-11, Vol.11 (1), p.5671-13, Article 5671

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Modelling oral squamous cell carcinoma (OSCC) is a complex endeavour. Here, the authors provide a comprehensive analysis of an OSCC mouse model and show its mutational signatures mirror human OSCC, providing insights into OSCC clonal dynamics, the microenvironment and evolution.