Plasma concentrations and cancer-associated mutations in cell-free circulating DNA of treatment-naive follicular lymphoma reveals possibility of improved non-invasive diagnosis and prognosis

Follicular lymphoma (FL) is a frequently observed type of indolent lymphoid cancer. The clinical phenotype of FL is highly heterogeneous, which includes asymptomatic as well as symptomatic cases. Furthermore, some FL cases may transition to aggressive B cell lymphomas with poor prognosis. Current evaluations routinely used in clinic for FL diagnosis or prediction of prognosis are generally based on invasive methodologies. There are several disadvantages of these invasive approaches including certain complications and pain felt by the patients. Recent studies in other cancer types showed that circulating cell-free DNA (cfDNA) genotyping may improve diagnosis as well as prognosis of patients by guiding therapy. Here, we showed that tumor tissue-derived, cancer-associated mutations can be detected by deep targeted sequencing of plasma cfDNA of FL patients. Our study revealed not only the possibility of detection of mutated genes (STAT6 or EZH2) in cfDNA which may be useful for choosing targeted therapy but also prognosis-associated mutations of BCL2 that can identify high risk groups especially with established clinical variables. This study also showed the possibility that histological transformation-associated gene variations may specifically be detected in plasma cfDNA samples. Blood samples can potentially be used as liquid biopsy for FL based on our observations.