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Lookup NU author(s): Dr Paul Milne, Dr Venetia BigleyORCiD, Professor Matthew CollinORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
OBJECTIVE: To identify a treatment-responsive BRAF(V600E) mutation in brainstem neurohistiocytosis, where no lesional tissue was readily obtainable, using a cell-free DNA approach. METHODS: Cell-free DNA was extracted from urine and allele-specific PCR for the BRAF(V600E) mutation was performed. Response to conventional treatment (corticosteroids and interferon) and targeted treatment with a BRAF inhibitor was assessed by clinical evaluation, gadolinium-enhanced MRI brain scan, and serial testing of urinary cell-free DNA for mutant alleles. RESULTS: BRAF(V600E) mutation could be readily identified in urinary cell-free DNA at an allele frequency of 4.2%. Treatment of Erdheim-Chester disease with corticosteroids and interferon was ineffective and associated with disease progression. Treatment with BRAF inhibitors was associated with clinical improvement and near-complete radiologic remission. Following 6 months of BRAF inhibitor therapy, no enhancing lesions could be detected in the brain and mutant alleles were cleared from the urine. CONCLUSIONS: Analysis of urinary cell-free DNA using allele-specific PCR for BRAF(V600E) mutations allows rapid noninvasive identification of a highly treatment-responsive pathway, leading to clinical and radiologic remission of disease. Our case demonstrates that this assay may have a particular role in challenging neurohistiocytosis cases, where attempts at obtaining lesional tissue have failed or are not feasible. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence. This is a single observation study without controls.
Author(s): Hunt D, Milne P, Fernandes P, Bigley V, Collin M
Publication type: Article
Publication status: Published
Journal: Neurology: Neuroimmunology & Neuroinflammation
Year: 2017
Volume: 4
Issue: 1
Online publication date: 01/01/2017
Acceptance date: 06/09/2016
Date deposited: 21/06/2017
ISSN (electronic): 2332-7812
Publisher: Wolters Kluwer Health
URL: https://doi.org/10.1212/NXI.0000000000000299
DOI: 10.1212/NXI.0000000000000299
PubMed id: 27833932
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