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: Julien Haroche, Frédéric Charlotte, Laurent Arnaud, Andreas von Deimling, Zofia Hélias-Rodzewicz, Baptiste Hervier, Fleur Cohen-Aubart, David Launay, Annette Lesot, Karima Mokhtari, Danielle Canioni, Louise Galmiche, Christian Rose, Marc Schmalzing, Sandra Croockewit, Marianne Kambouchner, Marie-Christine Copin, Sylvie Fraitag, Felix Sahm, Nicole Brousse, Zahir Amoura, Jean Donadieu, Jean-François Emile
• Journal: Blood (Blood) Vol. 120 Issue 13 Pg. 2700-3 (Sep 27 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22879539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Erdheim-Chester Disease (epidemiology, genetics)
• Female
• Follow-Up Studies
• France (epidemiology)
• Histiocytosis, Non-Langerhans-Cell (classification, epidemiology, genetics)
• Humans
• Male
• Middle Aged
• Mutation (genetics)
• Prevalence
• Prognosis
• Prospective Studies
• Proto-Oncogene Proteins B-raf (genetics)
• Young Adult