Detection of BRAF mutations in urine and plasma cell-free DNA: Application to the diagnosis and management of histiocytic disorder patients.

11012 Background: Histiocytosis patients (pts) have a high frequency of BRAFV600E mutations and respond to RAF inhibition but low tumor content and stromal contamination make detection in tissue biopsies challenging. Quantitative assessment of BRAFV600E mutations in tumor derived cell-free (cf) DNA may provide a convenient and reliable means of detecting this established biomarker and monitoring response to RAF targeted therapy. Here we compare the results of urine and plasma cfDNA BRAFV600E testing to tissue biopsy mutation testing in a large series of histiocytosis pts. Methods: Quantification of BRAFV600E was performed in cfDNA using droplet digital (dd) PCR (Trovagene, San Diego, CA). BRAFV600E analysis in tumor tissue was conducted using a variety of highly sensitive methodologies including locked nucleic acid and next-generation sequencing in CLIA-certified labs. Concordance between mutational analysis in tissue, plasma, and urine was determined. Results: 22 histiocytosis pts underwent cfDNA mutatio...