Centre for Stem Cells & Regenerative Medicine, King's College London, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
Nat Commun. 2020 Nov 9;11(1):5671. doi: 10.1038/s41467-020-19401-9.
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.
为了确定 4-硝基喹啉 N-氧化物诱导的致癌作用是否反映了人类口腔鳞状细胞癌（OSCC）的异质性，我们对小鼠舌病变进行了基因组分析。人类和小鼠 OSCC 的突变特征广泛重叠。中重度发育不良和浸润性 SCC 的突变负担高于增生和轻度发育不良，尽管 p53、Notch1 和 Fat1 中的突变发生在早期病变中。层粘连蛋白-α3 突变与肿瘤侵袭性相关，Notch1 突变肿瘤的免疫浸润增加。克隆动力学的计算模型表明，高遗传异质性可能是那些可能进展为更具侵袭性肿瘤的轻度发育不良的特征。这些研究为探索 OSCC 的进化、异质性和进展提供了基础。
