Although recent molecular analysis of human HNSCC cancer cell lines with and without NSD1 mutations (generated by CRISPR/Cas9 genome editing) revealed aberrant regulation of genes related to oxidative phosphorylation, MYC, mTORC1 or RAS signaling and other pathways, the impact on the cell biology has not been addressed and no particular transformation effector genes have been validated [65]. Here, NSD1 is linked to head and neck squamous cell carcinoma.