Analytical Validation and Clinical Sensitivity of the Belay Summit Assay for the Detection of DNA Variants in Cerebrospinal Fluid of Primary and Metastatic Central Nervous System Cancer

Sep 23, 2026

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Analytical Validation and Clinical Sensitivity describe the Belay Summit liquid biopsy assay designed for tumor-derived DNA from cerebrospinal fluid to support diagnosis of primary and metastatic central nervous system cancers. The assay shows analytical sensitivity of 96% for single-nucleotide/multinucleotide variants and insertions/deletions at a 0.30% variant allele fraction limit of detection, and 91% for chromosomal arm-level aneuploidy at abs(log2r) 0.09. In 124 specimens, clinical sensitivity is 90% with 95% specificity, supporting accurate and reproducible diagnostic use.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

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Purpose and clinical need

Analytical sensitivity performance

Clinical sensitivity and specificity

Clinical utility for CNS tumor diagnosis

The Journal of Molecular Diagnostics, Vol. 27, No. 7, July 2025 Analytical Validation and Clinical Sensitivity of the Belay Summit Assay for the Detection of DNA Variants in Cerebrospinal Fluid of Primary and Metastatic Central Nervous System Cancer Qian Nie, Kala F. Schilter, Kyle M. Hernandez, Jennifer N. Adams, Rakshitha Jagadish, Anthony Acevedo, Alexandra Larson, Brett A. Domagala, Samantha A. Vo, Sakshi Khurana, Kathleen Mitchell, Dean Ellis, Baymuhammet Muhammedov, Yuxuan Wang, Christopher Douville, Brian Coe, Chetan Bettegowda, and Honey V. Reddi From Belay Diagnostics, Chicago, Illinois Accepted for publication March 24, 2025 . Address correspondence to Honey V. Reddi, Ph.D., Belay Diagnostics, 1375 W. Fulton St., Chicago, IL 60607 . E-mail: hreddi@ [belaydiagnostics.com](belaydiagnostics.com). In contrast to most solid tumors, cancers of the central nervous system (CNS) pose a unique challenge for effective detection and tracking via plasma because of the blood-brain barrier. Informed diagnosis of primary and metastatic CNS tumors can be facilitated using a liquid biopsy assay that evaluates tumor-derived DNA from the cerebrospinal ﬂuid (CSF), potentially increasing the efﬁcacy of diagnosis and reducing the uncertainty and morbidities associated with the current standard of care that involves neurosurgical procedures. The Belay Summit assay involves tumor-derived DNAebased genomic proﬁling of CSF to inform diagnosis of CNS tumors. The analytical sensitivity of Summit for singlenucleotide/multinucleotide variants and insertions/deletions is 96% at a 95% limit of detection of 0.30% variant allele fraction. Analytical sensitivity for chromosomal arm-level aneuploidy is 91% at abs(log2r) of 0.09 limit of detection. Clinical sensitivity across a cohort of 124 specimens, including primary and metastatic CNS tumors, was demonstrated to be 90% with a speciﬁcity of 95%, supporting the potential for positive clinical utility. These results demonstrate that the Belay Summit assay can accurately and reproducibly be used to inform the diagnosis of primary and metastatic CNS tumors using CSF. (J Mol Diagn 2025, 27: 615e629; [https://doi.org/10.1016/j.jmoldx.2025.03.010](https://doi.org/10.1016/j.jmoldx.2025.03.010)) Progress in precision medicine has led to a dramatic increase in the development of molecular proﬁling assays for the identiﬁcation of biomarkers that can inform on diagnosis, prognosis, and targeted therapies. Genomic proﬁling of solid tissue obtain from biopsy or resection is now standard of care.1,2 In recent years, liquid biopsy using plasma/serum has been extensively used for early detection and monitoring of minimal residual disease, development of resistance to therapy, or recurrence of disease in solid tumors.3 In contrast to most solid tumors, cancer of the central nervous system (CNS) poses a unique challenge for effective detection and tracking via plasma because of the bloodbrain barrier, which signiﬁcantly lowers the amounts of circulating nucleic acids shed by brain tumors.4 Recent studies have shown that liquid biopsy using cerebrospinal ﬂuid (CSF) could serve as an effective surrogate to inform diagnosis of primary and metastatic CNS cancers.5e12 Current standard of care for diagnosis and detection of CNS tumors includes magnetic resonance imaging, which can be non-speciﬁc,13, 14 and CSF cytology, 15, 16 which requires substantial volume (>10 mL) of CSF and has low sensitivity (41%) because of the absence of genomic interrogation.17 Because CSF is often assessed for cytology, a CSFetumor-derived DNA (tDNA) assay can be incorporated into the testing/evaluation algorithm using a portion of Supported in part by NIH grant 1R42NS135834-01 (B.C.) . Q.N. and K.F.S. contributed equally to this work. The contents of the publication are solely the responsibility of the authors and do not necessarily represent the ofﬁcial views of the NIH. Copyright ª 2025 Association for Molecul

FAQs

What problem does the Belay Summit assay address for CNS tumors?

It targets the diagnostic challenge posed by the blood-brain barrier, which limits circulating nucleic acids in plasma, by using tumor-derived DNA from cerebrospinal fluid.

What analytical sensitivity does the assay achieve for DNA variants?

For single-nucleotide/multinucleotide variants and insertions/deletions, it reports 96% analytical sensitivity at a 0.30% variant allele fraction limit of detection.

How did clinical sensitivity and specificity perform in the study cohort?

Across 124 specimens, clinical sensitivity was 90% with specificity of 95%, indicating potential positive clinical utility.

Sep 23, 2026

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