Abstract
Erdheim-Chester disease (ECD) is a rare histiocytosis with a high prevalence of BRAF V600E mutation (>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 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.
Highlights
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis affecting adults, which is associated with xanthogranulomatous infiltration of foamy macrophages.[1,2,3]
Advances in genome sequencing technologies led to the identification of BRAF V600E mutations in at least 50% of patients with ECD.[4]
The concept of mutation testing from urine cell-free DNA (cfDNA) has been assessed in a pilot study in patients with advanced colorectal cancer and other colorectal diseases in which KRAS mutations in urine cfDNA were concordant in 95% of cases with KRAS mutation status in tumor tissue.[15]
Summary
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis affecting adults, which is associated with xanthogranulomatous infiltration of foamy macrophages.[1,2,3] ECD is deemed to be driven by increased signaling within the mitogen-activatedprotein kinase pathway. Cell-free DNA (cfDNA) is released to the circulation from cells undergoing apoptosis, necroptosis and active secretion and has been identified in the plasma and urine of patients with cancer.[7, 8] Detecting and quantifying the amount of mutant cfDNA fragments harboring specific mutations can be used as an alternative to tissue testing.
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