LAUSR

MYD88L265P and CXCR4S338X variants are highly prevalent and impact disease presentation, prognosis, and/or treatment outcome in Waldenstrom's Macroglobulinemia (WM). The use of bone marrow (BM) aspirate represents the current "gold standard" for molecular testing in WM. Although these variants are identified in peripheral blood (PB), the diagnostic yield in PB is inferior to BM, particularly for previously treated patients. Tumor enrichment can significantly improve testing sensitivity, but is not feasible in most clinical laboratories. Recent studies have demonstrated the feasibility of identifying MYD88 and CXCR4 mutations using cell-free DNA (cfDNA) from the plasma of WM patients. We therefore prospectively collected matched BM and PB samples from 28 consecutive WM patients. Overall, five different tissue fractions were isolated for analysis: CD19-selected BM, unselected BM, CD19-selected PB, unselected PB, and cfDNA. Quantitative allele-specific polymerase chain reaction assays for MYD88L265P and CXCR4S338X mutations were performed for each tissue fraction, and findings benchmarked against CD19-selected BM. Both MYD88L265P and CXCR4S338X were identified with high sensitivity and specificity in cfDNA derived from the plasma of WM patients, including previously treated patients. The use of cfDNA represents a non-invasive, convenient, and potentially cost-effective method for genotyping patients with WM. This article is protected by copyright. All rights reserved.