title: Genomic Alterations in Langerhans Cell Histiocytosis.
abstract: The discovery of recurrent somatic genomic alterations in Langerhans cell histiocytosis (LCH) has led to a new understanding of LCH as a clonal neoplastic disorder. Most of the abnormalities described to date affect the RAS/RAF/MEK/extracellular-signal-regulated kinase (ERK) pathway: more than 50% of LCH cases carry activating mutations in BRAF, whereas another 10% to 28% carry activating mutations of MAP2K1, which encodes MEK1. The pathogenetic importance of these mutations has been confirmed by reports of significant clinical responses to RAF inhibitors.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: barrett_rollins@dfci.harvard.edu.
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
mesh_terms: D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D058990:Molecular Targeted Therapy; D009154:Mutation
keywords: BRAF; LCH; Langerhans cell histiocytosis; MAP2K1; MEK1