The characterization of circulating
tumor-derived
DNA (ctDNA) has recently emerged in the field of oncology as a powerful method to identify
tumor-specific genetic aberrations using peripheral blood testing. Several technical precautions are needed at the pre-analytic stage (given the short half-life of free
nucleic acids in plasma), and numerous techniques-with different sensitivities-are available to identify these molecular aberrations, ranging from the detection of single point mutations to extended genetic screening panels. Although a "liquid biopsy" cannot be substituted for the pathological examination of tissue specimens for diagnostic purposes, it can sometimes
complement pathology results or serve as a proxy approach for particular
lymphoma presentations where biopsies are sometimes difficult to perform. Moreover, ctDNA testing can characterize, at diagnosis or during treatment, mutations that may contribute to the choice of an optimal targeted
therapy (such as
Bruton tyrosine kinase or EZH2 inhibitors) or detect the emergence of resistance to those
therapies. High levels of ctDNA before treatment appear to be correlated with advanced disease stages and prognosis in diffuse large B-cell and
follicular lymphomas. Real-time follow-up of ctDNA levels during
therapy in several
lymphoma subtypes (diffuse large B-cell and Hodgkin
lymphomas) has been explored: preliminary studies have demonstrated that this monitoring technique can predict clinical outcomes (end of treatment response and risk of progression
after treatment completion) and that this approach may
complement the information provided by metabolic imaging assessments. Technical standardization and careful prospective evaluation of the role of ctDNA monitoring in clinical studies represent current important challenges to allowing its application in routine practice.