Ann Lab Med.  2025 Jan;45(1):90-95. 10.3343/alm.2024.0257.

Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma

• Kim SJ
• Kim JJ
• Park MR
• Park B
• Ryu KJ
• Yoon SE
• Kim WS
• Shin S
• Lee ST

• KMID: 2563860
• DOI: http://doi.org/10.3343/alm.2024.0257

Abstract

We explored the utility of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) sequencing as a noninvasive diagnostic tool for detecting central nervous system (CNS) involvement in patients with diffuse large B-cell lymphoma (DLBCL). Secondary CNS involvement in DLBCL, although rare (~5% of cases), presents diagnostic and prognostic challenges during systemic disease progression or relapse. Effective treatment is impeded by the blood–brain barrier. This was a prospective cohort study (Samsung Lymphoma Cohort Study III) involving 17 patients with confirmed CNS involvement. High-throughput sequencing was conducted using targeted gene panels designed to detect low-frequency variants and copy number alterations pertinent to lymphomas in ctDNA extracted from archived CSF samples. Despite challenges such as low DNA concentrations affecting library construction, the overall variant detection rate was 76%. Detected variants included those in genes commonly implicated in CNS lymphoma, such as MYD88. The study highlights the potential of CSF ctDNA sequencing to identify CNS involvement in DLBCL, providing a promising alternative to more invasive diagnostic methods such as brain biopsy, which are not always feasible. Further validation is necessary to establish the clinical utility of this method, which could significantly enhance the management and outcomes of DLBCL patients with suspected CNS involvement.

Keyword

Central nervous system; Cerebrospinal fluid; Circulating tumor DNA; Lymphoma; Relapse

Figure

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  Fig. 1 Study flow. Abbreviations: CNS, central nervous system; CSF, cerebrospinal fluid.

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  Fig. 2 Mutation profiles and DNA concentration distribution in CSF from patients with CNS involvement. (A) Mutation profiles detected in ctDNA from 14 patients. (B) Consistency of mutation profiles in serial samples of two patients (No. 9 and 16). (C) DNA concentration distribution according to the status of ctDNA detection. Abbreviations: ctDNA, circulating tumor DNA; CSF, cerebrospinal fluid; CNS, central nervous system.

Reference

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