Abstract
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 based EZH2 mutation analysis performed by a highly sensitive droplet digital PCR method may be a valuable treatment monitoring approach in EZH2 mutant follicular lymphoma. EZH2 variant 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 of EZH2 mutations decreased or were eliminated rapidly upon successful treatment, with treatment failure being associated with elevated EZH2 variant allele frequencies. We also demonstrated spatial heterogeneity in a patient with two different EZH2 mutations in distinct anatomical sites, with both mutations simultaneously detected in the liquid biopsy specimen. In summary, circulating tumor DNA based EZH2 mutation analysis offers a rapid, real-time, radiation-free monitoring tool for sensitive detection of EZH2 mutations deriving from different anatomical sites in follicular lymphoma patients receiving immunochemotherapy.
Highlights
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) among adults in developed countries [1,2]
Liquid biopsy-based mutation analysis is becoming a valuable tool for cancer detection and sensitive disease monitoring
We present four cases of EZH2 mutant FLs, where circulating tumor DNA (ctDNA) based treatment monitoring was performed using a highly sensitive ddPCR method to detect EZH2 mutations in patients treated with ICT
Summary
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) among adults in developed countries [1,2]. Genes 2020, 11, 785 generating a need to develop sensitive and broadly accessible tools for disease monitoring. As relapsed and transformed FL is characterized by decreased sensitivity to immunochemotherapeutic regimens, development of new treatment modalities represents an unmet clinical need. Liquid biopsy is a novel and emerging radiation-free technique to noninvasively monitor patients with malignant disease and to evaluate their response to treatment [11,12]. Investigating circulating tumor DNA (ctDNA) in patient derived plasma using highly sensitive technologies may overcome the limitations of the other patient evaluating tools mentioned above, as it is less invasive, radiation-free, quick, sensitive and capable of conveying genetic information from a spatially heterogeneous or disseminated tumor [13]
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