Circulating tumor DNA from blood and cerebrospinal fluid in DLBCL: simultaneous evaluation of mutations, IG rearrangement, and IG clonality.

Abstract

Background: Circulating tumor DNA (ctDNA) is a promising biomarker for monitoring minimal residual disease (MRD), assessing disease status, and guiding treatment in diffuse large B-cell lymphoma (DLBCL). Current ctDNA assays rarely detect immunoglobulin (IG) fusions. This study evaluates a novel assay that simultaneously detects mutations, IG fusions, and IG V(D)J clonality in plasma and cerebrospinal fluid (CSF) to enhance molecular profiling and CNS monitoring.

Methods: A prospective analysis was conducted in 57 DLBCL patients. Genomic alterations in plasma and CSF ctDNA were compared to those in tumor tissue using targeted next-generation sequencing (NGS).

Results: Mutations, IG fusions, and IG V(D)J clonality were detected in 100%, 72.2%, and 78.6% of plasma ctDNA samples, respectively. Plasma ctDNA also revealed additional mutations absent in tumor tissue, reflecting clonal heterogeneity. The incorporation of IG fusion detection enabled molecular subtyping without requiring FISH. In CSF, ctDNA analysis identified genomic alterations in 8 cases, whereas conventional imaging and cytology confirmed CNS involvement in only 3, demonstrating the superior sensitivity of ctDNA for CNS surveillance.

Conclusion: This ctDNA assay offers a non-invasive, integrated approach for genomic profiling and disease monitoring in DLBCL, with improved sensitivity for CNS detection and potential to inform personalized treatment strategies.