Dataset Information

Targeted treatment of brainstem neurohistiocytosis guided by urinary cell-free DNA.

ABSTRACT:

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.

SUBMITTER: Hunt D

PROVIDER: S-EPMC5096418 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeted treatment of brainstem neurohistiocytosis guided by urinary cell-free DNA.

Hunt David D Milne Paul P Fernandes Peter P Bigley Venetia V Collin Matthew M

Neurology(R) neuroimmunology & neuroinflammation 20161103 1

<h4>Objective</h4>To identify a treatment-responsive <i>BRAF</i><sup><i>V600E</i></sup> mutation in brainstem neurohistiocytosis, where no lesional tissue was readily obtainable, using a cell-free DNA approach.<h4>Methods</h4>Cell-free DNA was extracted from urine and allele-specific PCR for the <i>BRAF</i><sup><i>V600E</i></sup> mutation was performed. Response to conventional treatment (corticosteroids and interferon) and targeted treatment with a BRAF inhibitor was assessed by clinical evalua ...[more]

PMID: 27833932

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Dataset Information

Targeted treatment of brainstem neurohistiocytosis guided by urinary cell-free DNA.

Objective

Methods

Results

Conclusions

Classification of evidence

Publications

Targeted treatment of brainstem neurohistiocytosis guided by urinary cell-free DNA.

Similar Datasets

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