title: High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses.
abstract: Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis (LCH). We investigated the frequency of BRAF mutations in several types of histiocytoses. Histology from 127 patients with histiocytoses were reviewed. Detection of BRAF(V600) mutations was performed by pyrosequencing of DNA extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma, xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients, respectively. BRAF status was obtained in 93 cases. BRAF(V600E) mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses. Four patients with ECD died of disease. The high frequency of BRAF(V600E) in LCH and ECD suggests a common origin of these diseases. Treatment with vemurafenib should be investigated in patients with malignant BRAF(V600E) histiocytosis.
authors.affiliation: Department of Internal Medicine & French Reference Center for Rare Auto-immune & Systemic Diseases, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Zofia
authors.initials: Z
authors.lastname: Hélias-Rodzewicz
authors.forename: Baptiste
authors.initials: B
authors.lastname: Hervier
authors.forename: Fleur
authors.initials: F
authors.lastname: Cohen-Aubart
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.forename: Annette
authors.initials: A
authors.lastname: Lesot
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Louise
authors.initials: L
authors.lastname: Galmiche
authors.forename: Christian
authors.initials: C
authors.lastname: Rose
authors.forename: Marc
authors.initials: M
authors.lastname: Schmalzing
authors.forename: Sandra
authors.initials: S
authors.lastname: Croockewit
authors.forename: Marianne
authors.initials: M
authors.lastname: Kambouchner
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraitag
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D031249:Erdheim-Chester Disease / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D015616:Histiocytosis, Non-Langerhans-Cell / Q000145:classification* / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf