Potential clinical implications of BRAF mutations in histiocytic proliferations

52Citations
Citations of this article
36Readers
Mendeley users who have this article in their library.

Abstract

For a growing number of tumors the BRAF V600E mutation carries therapeutic relevance. In histiocytic proliferations the distribution of BRAF mutations and their relevance has not been clarified. Here we present a retrospective genotyping study and a prospective observational study of a patient treated with a BRAF inhibitor. Genotyping of 69 histiocytic lesions revealed that 23/48 Langerhans cell lesions were BRAF-V600E-mutant whereas all non-Langerhans cell lesions (including dendritic cell sarcoma, juvenile xanthogranuloma, Rosai-Dorfman disease, and granular cell tumor) were wild-type. A metareview of 29 publications showed an overall mutation frequency of 48.5%; and with N=653 samples, this frequency is well defined. The BRAF mutation status cannot be predicted based on clinical parameters and outcome analysis showed no difference. Genotyping identified a 45 year-old woman with an aggressive and treatment-refractory, ultrastructurally confirmed systemic BRAF-mutant LCH. Prior treatments included glucocorticoid/vinblastine and cladribine-monotherapy. Treatment with vemurafenib over 3 months resulted in a dramatic metabolic response by FDG-PET and stable radiographic disease; the patient experienced progression after 6 months. In conclusion, BRAF mutations in histiocytic proliferations are restricted to lesions of the Langerhans-cell type. While for most LCH-patients efficient therapies are available, patients with BRAF mutations may benefit from the BRAF inhibitor vemurafenib.

Cite

CITATION STYLE

APA

Bubolz, A. M., Weissinger, S. E., Stenzinger, A., Arndt, A., Steinestel, K., Brüderlein, S., … Lennerz, J. K. (2014). Potential clinical implications of BRAF mutations in histiocytic proliferations. Oncotarget, 5(12), 4060–4070. https://doi.org/10.18632/oncotarget.2061

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free