Interestingly, three class of hallmark genes involved in HNSCC could be distinctly identified: genes that are primarily altered by mutations like TP53 and SYNE1; genes that are sparsely altered by amplification or overexpression in addition to mutations like FAT1, NOTCH1, KMT2D, and FLG; and, genes that are preferentially altered by amplification or over expression over point mutations with higher cumulative effect than known before. The gene discussed is KMT2D; the disease is head and neck squamous cell carcinoma.