Reliable detection of CNS lymphoma-derived circulating tumor DNA in cerebrospinal fluid using multi-biomarker NGS profiling: insights from a real-world study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F25%3A00082034" target="_blank" >RIV/65269705:_____/25:00082034 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/25:00141254

Result on the web

<a href="https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00777-z" target="_blank" >https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00777-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s40364-025-00777-z" target="_blank" >10.1186/s40364-025-00777-z</a>

Result language

angličtina

Original language name

Reliable detection of CNS lymphoma-derived circulating tumor DNA in cerebrospinal fluid using multi-biomarker NGS profiling: insights from a real-world study

Original language description

Background Diagnosing primary or secondary CNS lymphoma (CNSL) is a clinical challenge due to the limitations of standard biopsy and imaging procedures despite established guidelines. Therefore, accurate biomarkers and analytical methods that are convenient for practical routine use are needed to diagnose and manage these aggressive lymphomas effectively. We evaluated the utility of minimally invasive circulating tumor DNA (ctDNA) detection in a prospective real-world scenario, moving this approach closer to clinical practice. Methods A total of 164 plasma, cerebrospinal fluid (CSF), and tumor samples from 56 CNSL patients were collected to analyze tumor DNA by the diagnostic next-generation sequencing (NGS) panel LYNX, enabling simultaneous analysis of gene variants, chromosomal aberrations, and antigen receptor rearrangements in targeted regions. Results The well-known genetic heterogeneity of CNSL was refined with integrative molecular data, showing the most frequent MYD88, PIM1, and KMT2D mutations and a broad spectrum of chromosomal aberrations, reflecting high genomic complexity. The multi-target approach achieved a substantially higher detection rate of CNS infiltration (90%) than tracking a single variant in gene MYD88 (46%). CSF clearly surpasses plasma if applying a routine (non-ultrasensitive) NGS approach and allows for more reliable evidence of CNS involvement than conventional flow cytometry (91% vs. 21%, p &lt; 0.001). Parallel analysis of tumor DNA in both cell-free and cellular DNA from CSF makes the probability of primary or secondary CNS malignancy detection even higher. Conclusions Our prospective, tissue-agnostic approach highlights the feasibility of ctDNA sequencing by a commonplace and affordable method, offering higher sensitivity to detect CNS infiltration with lymphoma than standard cell-analyzing techniques. We accentuate the benefit of a multi-target NGS approach and adequate CSF sampling to obtain satisfactory diagnostic yield. Less invasive liquid biopsy testing by comprehensive NGS complements standard procedures in the diagnostics and management of CNSL patients, especially when encountering limitations.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biomarker Research

ISSN

2050-7771

e-ISSN

2050-7771

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

71

UT code for WoS article

001485606600001

EID of the result in the Scopus database

2-s2.0-105004890394