<i>BRAF</i> V600E mutations in urine and plasma cell-free DNA from patients with Erdheim-Chester disease

Abstract

// Filip Janku 1 , Cecile Rose T. Vibat 2 , Karena Kosco 2 , Veronica R. Holley 1 , Goran Cabrilo 1 , Funda Meric-Bernstam 1 , Vanda M. Stepanek 1 , Patrick P. Lin 3 , Lorieta Leppin 2 , Latifa Hassaine 2 , Jason C. Poole 2 , Razelle Kurzrock 4 and Mark G. Erlander 2 1 Department of Investigational Cancer Therapeutics, The University of Texas&nbsp;MD Anderson Cancer Center 2 Trovagene Inc. San Diego, CA 3 Department of Orthopedic Oncology, The University of Texas&nbsp;MD Anderson Cancer Center 4 Moores Cancer Center, The University of California San Diego, La Jolla, CA Correspondence: Filip Janku, email: // Keywords : BRAF, cell-free DNA, plasma, urine, Erdheim-Chester disease Received : March 12, 2014 Accepted : May 12, 2014 Published : May 13, 2014 Abstract Erdheim-Chester disease (ECD) is a rare histiocytosis with a high prevalence of BRAF V600E mutation (&gt;50% of patients). Patients with BRAF -mutant ECD can respond to BRAF inhibitors. Unfortunately, the lack of adequate archival tissue often precludes BRAF testing. We hypothesized that cell-free DNA (cfDNA) from plasma or urine can offer an alternative source of biologic material for testing. We tested for&nbsp; BRAF V600E mutation in cfDNA from the plasma and urine of 6 ECD patients. In patients with available archival tissue, the result of BRAF mutation analysis was concordant with plasma and urine cfDNA results in all 3 patients (100% agreement, kappa 1.00). In all 6 patients, BRAF mutation analysis of plasma and urine cfDNA was concordant in 5 of 6 patients (83% agreement, kappa 0.67). Testing for BRAF V600E mutation in plasma and urine cfDNA should be further investigated as an alternative to archival tissue mutation analysis.