Known recurrent cancer genes include PCLO, FAT3, SMG1, MLL2, SYNE2, and EP300. Pathways enriched for genomic alterations, such as the Wnt signaling pathway, the dorsoventral axis formation pathway, and the axon guidance pathway, have not been previously reported in HNSCC and therefore are considered specific for oral and gingivo-buccal SCCs [11]. Here, KMT2D is linked to head and neck squamous cell carcinoma.