Liquid biopsy in lymphoma

Abstract

The term “liquid biopsy” means accessing tumor DNA through a blood sampling, without the need of an invasive tissue biopsy. Cell-free fragments of DNA (cfDNA) are shed into the bloodstream by cells undergoing apoptosis and circulate at a low concentration in plasma as double-stranded DNA fragments that are predominantly short (<200 base pairs).1 In healthy subjects, cfDNA primarily derives from the apoptosis of cells of hematopoietic lineage, with minimal contributions from other tissues, and circulates in concentrations of 1-10 ng/mL of plasma.2-8 In lymphoma patients, a proportion of cfDNA derives from apoptotic tumor cells.5 The total amount of cfDNA in lymphoma patients is always increased compared with age-and gender-matched healthy subjects, with a mean concentration of 30 ng/mL of plasma.9-12 Levels of circulating tumor DNA (ctDNA) vary across different lymphoma subtypes, being higher in aggressive lymphomas than in indolent lymphomas. Beside lymphoma type, tumor volume also affects cfDNA levels, which are higher in advanced stage disease than in limited stage disease, and in overt progressive disease than in a disease that is clinically responding to treatment.9,11 This perspective aims at describing the unmet needs in the field of diagnosis, genotyping, and assessment of treatment response in lymphomas that can be addressed by ctDNA technologies, as well as current evidence, and/or further investigations or actions that would be needed before transferring ctDNA technologies into the clinic.