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Updated: Mar 12, 2026
Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
Published on: November 14, 2013
Targeted treatment of brainstem neurohistiocytosis guided by urinary cell-free DNA
David Hunt1, Paul Milne1, Peter Fernandes1
1MRC Institute of Genetics and Molecular Medicine (D.H.) and Anne Rowling Neurology Clinic, Centre for Clinical Brain Sciences (D.H., P.F.), University of Edinburgh; and Human Dendritic Cell Laboratory (P.M., V.B., M.C.), Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne UK.
Objective:
To identify a treatment-responsive BRAFV600E 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 BRAFV600E 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:
BRAFV600E 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 BRAFV600E 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.
