Schematic depiction of mutations in NOTCH1. (A) Previously observed NOTCH1 mutations in hematopoietic malignancies. EGF = Epidermal growth factor, LNR = Lin12-Notch repeats, TMD = trans-membrane domain, RAM = Recombination signal-binding protein 1 for J-Kappa (RBPjk) association module, NLS = nuclear localization signal, PEST = proline, glutamic acid, serine/threonine-rich motifs. Red bars represent previously described mutation hotspots (amino acids 1575–1630 and 2250–2550). (B) Previously observed NOTCH1 mutations in solid tumors. Colored arrow (missense mutation) and “X” (truncating mutation) depict mutations found in different tumor types: pink = breast cancer, black = glioma, blue = lung cancer, green = pancreatic adenocarcinoma, red = esophageal squamous cell carcinoma, purple = tongue squamous cell carcinoma. (C) Mutations in NOTCH1 in HNSCC observed in this study. Black arrow = missense mutation, red “X” = truncating mutation (13, 22–24).