Quantitative Analysis and Monitoring of EZH2 Mutations Using Liquid Biopsy in Follicular Lymphoma

Recent advances in molecular technologies enable sensitive and quantitative assessment of circulating tumor DNA, offering a noninvasive disease monitoring tool for patients with malignant disorders. Here, we demonstrated on four follicular lymphoma cases that circulating tumor DNA basedEZH2mutation analysis performed by a highly sensitive droplet digital PCR method may be a valuable treatment monitoring approach inEZH2mutant follicular lymphoma.EZH2variant allele frequencies changed in parallel with the volume of metabolically active tumor sites observed on 18F-fluorodeoxyglucose positron emission tomography combined with computer tomography (PET-CT) scans. Variant allele frequencies ofEZH2mutations decreased or were eliminated rapidly upon successful treatment, with treatment failure being associated with elevatedEZH2variant allele frequencies. We also demonstrated spatial heterogeneity in a patient with two differentEZH2mutations in distinct anatomical sites, with both mutations simultaneously detected in the liquid biopsy specimen. In summary, circulating tumor DNA basedEZH2mutation analysis offers a rapid, real-time, radiation-free monitoring tool for sensitive detection ofEZH2mutations deriving from different anatomical sites in follicular lymphoma patients receiving immunochemotherapy.