Recent profiling studies in head-and-neck SCC emphasize recurrent UV-signature mutations (C > T transitions) involving key tumor suppressor genes such as TP53 and CDKN2A, along with alterations in NOTCH1/2 and HRAS, converging on p53, cell-cycle, RTK/RAS and PI3K signaling pathways. The gene discussed is TP53; the disease is neoplasm.