We have found that the mutational spectrum of human OSCC is faithfully recapitulated in 4NQO-induced mouse tumours, including mutations in Trp53, Pik3ca, Notch1, Fat1, Lama3 and Syne2. In addition, we provide a comprehensive analysis of the genomic landscape of 4NQO carcinogenesis at different stages of tumour development, from early hyperplasia to invasive SCC. Here, FAT1 is linked to neoplasm.