Recently, whole exome sequencing of HNSCC revealed that dysregulation of NOTCH1, IRF6, and TP63, which regulate squamous differentiation, is a driver of HNSCC carcinogenesis, similar to mutations of TP53, CDKN2A, PTEN, PIK3CA, and HRAS [7, 8]. The gene discussed is NOTCH1; the disease is head and neck squamous cell carcinoma.