Liquid biopsy in lymphomas: a potential tool for refining diagnosis and disease monitoring

Liquid biopsy consists in a simple blood sampling that allows to analyze cell free DNA (cfDNA), containing specific genomic clues released by the tumor into the bloodstream. In this review, we shall focus on the analysis of cfDNA in lymphoma and, in particular, on its application in the genotyping and monitoring of two common types of B-cell lymphoma, i.e., diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). From a diagnostic standpoint and based upon the current international guidelines, lymphoma diagnosis has so far relied on the analysis of the tissue biopsy. From a molecular viewpoint, though, the tissue biopsy does not reflect the entire molecular heterogeneity of lymphomas. In fact, in an individual patient, lymph nodes at different anatomical sites, as well as different areas of the same lymph node, may show different genetic profiles. Consequently, molecular analysis of genomic DNA extracted from a single lymph node biopsy may not recapitulate the whole mutational landscape of the disease. Liquid biopsy may overcome this hurdle, since cfDNA is released by all tumoral cells and can reveal the entire molecular complexity of lymphomas. From a translational perspective, liquid biopsy may also be used to evaluate clonal evolution, response to therapy and minimal residual disease. Consistently, in DLBCL as well in cHL, the drop of the mutational burden during the treatment course provides complementary information to conventional imaging techniques. The integration of liquid biopsy with imaging techniques may prove useful for a better prediction of patients' outcome and for a better treatment tailoring.