Data from Prospective Blinded Study of <i>BRAF</i><sup>V600E</sup> Mutation Detection in Cell-Free DNA of Patients with Systemic Histiocytic Disorders

Abstract

<div>Abstract<p>Patients with Langerhans cell histiocytosis (LCH) and Erdheim–Chester disease (ECD) have a high frequency of <i>BRAF</i><sup>V600E</sup> mutations and respond to RAF inhibitors. However, detection of mutations in tissue biopsies is particularly challenging in histiocytoses due to low tumor content and stromal contamination. We applied a droplet-digital PCR assay for quantitative detection of the <i>BRAF</i><sup>V600E</sup> mutation in plasma and urine cell-free (cf) DNA and performed a prospective, blinded study in 30 patients with ECD/LCH. There was 100% concordance between tissue and urinary cfDNA genotype in treatment-naïve samples. cfDNA analysis facilitated identification of previously undescribed <i>KRAS</i><sup>G12S</sup>-mutant ECD and dynamically tracked disease burden in patients treated with a variety of therapies. These results indicate that cfDNA <i>BRAF</i><sup>V600E</sup> mutational analysis in plasma and urine provides a convenient and reliable method of detecting mutational status and can serve as a noninvasive biomarker to monitor response to therapy in LCH and ECD.</p><p><b>Significance:</b> Patients with <i>BRAF</i><sup>V600E</sup>-mutant histiocytic disorders have remarkable responses to RAF inhibition, but mutation detection in tissue in these disorders is challenging. Here, we identify that analysis of plasma and urinary cfDNA provides a reliable method to detect the <i>BRAF</i><sup>V600E</sup> mutation and monitor response to therapy in these disorders. <i>Cancer Discov; 5(1); 64–71. ©2014 AACR</i>.</p><p>This article is highlighted in the In This Issue feature, p. 1</p></div>