Similar connections emerge between Notch signalling activities and mutations in histone methylation-related genes such as the lysine methyltransferase 2, also known as MLL-1, KMT2A/MLL-1, and other members of the KMT gene family, such as KMT2C and D, are frequently mutated in HNSCC and show an interesting positive correlation with the presence of Notch mutations (Figure 1B). The gene discussed is KMT2A; the disease is head and neck squamous cell carcinoma.