The clinical value of circulating free tumor DNA in testicular germ cell tumor patients

Background: Testicular germ cell tumors (TGCT) are unique malignancies of young adult men; their biology is, however, underex-plored and there has not been much progress in their treatment for decades. Circulating free tumor DNA (cfDNA) analysis represents a promising way of discovering novel diagnostic and treatment options. Objective: The study evaluates the clinical value of cfDNA detection in TGCT patients. Design and Methods: Total cfDNA concentration and ratio of its 2 main fragments (180 and 360 bp) were evaluated by spectrophotom-etry, capillary electrophoresis and qPCR in peripheral blood plasma of 96 TGCT patients (173 samples) and 31 normal controls. Non -parametric tests were used for statistical analyses. Results: The total cfDNA concentration was significantly higher in TGCT than in controls (P < 0.0001), with the highest levels at dis-ease progression, but with no clear threshold between malignant and normal samples. Patients with positive tumor markers had higher cfDNA concentrations than those with negative markers (P = 0.01). Longer 360 bp cfDNA fragments were found in 58% of TGCT patients including almost all samples from relapse or disease progression but no normal controls (P < 0.0001). Conclusion: Total cfDNA levels are significantly increased in TGCT patients but without a clear threshold separating normal and tumor samples, thus total cfDNA amount itself is not a sensitive enough marker to identify or monitor TGCT. Longer cfDNA fragments have been found exclusively in a proportion of tumors and predominantly at disease progression, representing a novel potential marker for TGCT monitoring that would deserve further exploration. (C) 2022 Elsevier Inc. All rights reserved.