Somatic MAP2K1 mutations in LCH. (A) The frequency of mutually exclusive BRAF and MAP2K1 mutations in LCH is shown. (B) A portion of the MAP2K1 gene including exons 2 and 3 is depicted at the bottom, and regions of the MEK1 protein encoded by exons 2 and 3 are depicted above. Somatic mutations in LCH involve the N-terminal negative regulatory region encoded by exon 2 and the catalytic core encoded by exon 3. The circles above the protein denote substitutions and the bars below the protein indicate in-frame deletions. (C) A sequence electropherogram from case 26 (top) demonstrates the most common mutation identified in this study, E102_I103del. The absence of this mutation in a sequence electropherogram from matched constitutional DNA (bottom) confirms the somatic nature of this mutation. (D) Sequence electropherograms from case 32 (top) and matched constitutional DNA (bottom) demonstrate 2 somatic missense mutations—C121S and G128V—at similar allele frequencies.