MAPK pathway mutations identified in LCH patients. (A) Location of somatic MAP2K1 mutations identified in LCH patients in this study (top) and reported in other malignancies in the COSMIC database and recent literature (bottom). Also depicted in black are germ-line mutations observed in cardio-facio-cutaneous (CFC) syndrome. Triangles and bars indicate missense and in-frame deletion mutations, respectively. Figure not to scale. (B) Somatic mutations identified in multiple MAPK pathway members in LCH patients. C, carboxyl; D, docking; Mg, magnesium positioning loop; N, peptidyl; NES, nuclear export signal; NRR, negative regulatory region; P, phosphate binding; Pro, proline.