What question did this study set out to answer?

April 19, 2026Open Access

Clinical Validation of the Belay Ascent™ Test to Report on Chromosomal Arm-Level Aneuploidy and Gene-Level Copy Number Variants in Cerebrospinal Fluid Using Low-Pass Whole-Genome Sequencing

QNQian NieCS Diagnostics KSKala F. SchilterUniversity of Chicago ALAlexandra Larson

Key Points

To validate the Belay Ascent™ test for detecting chromosome arm-level aneuploidy and gene-level copy number variants in cerebrospinal fluid.
Evaluated 48 tissue specimens to establish equivalence for detecting aneuploidy and CNVs.
Conducted clinical validation with a cohort of 32 cerebrospinal fluid specimens.
Compared results to gold standard methods like chromosomal microarray and next-generation sequencing.
100% positive percent agreement for aneuploidy and 97% for gene-level CNVs in tissue specimens.
In CSF specimens, the positive percent agreement was 78% for aneuploidy and 90% for gene-level CNVs.
The test informed diagnosis and management in 243 production cases with high accuracy.

Abstract

Background: Evaluation of chromosome aneuploidy and gene-level copy number alterations for diagnosis, prognosis, and therapeutic decision-making in solid tumors is the standard of care. Chromosomal microarray (CMA), next-generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) are the gold standard for detecting these variants in tumor tissue. In contrast to most solid tumors, cancers of the central nervous system (CNS) pose a unique challenge for effective detection via plasma due to the blood–brain barrier (BBB), with the additional challenges of brain biopsy or surgery being highly invasive and posing a significant risk to the patient. The Belay Ascent™ liquid biopsy test uses low-pass whole-genome sequencing (LP-WGS) to report on chromosome arm-level aneuploidy and gene-level copy number variants (CNVs) in cerebrospinal fluid (CSF) to inform diagnosis, prognosis, and therapeutic decision-making in CNS tumors. Methods: This study presents the equivalence of Ascent™ in detecting chromosome arm-level aneuploidy and gene-level CNVs using 48 tissue specimens followed by a clinical validation using a cohort of 32 CSF specimens with matched tissue-based tumor profiling information. Results: Equivalence of Ascent™ in detecting chromosome arm-level aneuploidy and gene-level CNVs using 48 tissue specimens was shown to have 100% and 97% positive percent agreement (PPA), respectively, compared to the gold standard of CMA/NGS. The validation cohort of 32 CSF specimens demonstrated 78% and 90% PPA for aneuploidy and gene-level CNVs, respectively. Clinical impact of Ascent™ was demonstrated, with 243 production cases able to inform the diagnosis and management of CNS tumors with high accuracy. Conclusions: Given the paucity of cells in CSF, limiting the use of karyotyping, CMA, IHC, and FISH, the Belay Ascent™ test provides a highly sensitive novel minimally invasive method for the evaluation of chromosome aneuploidy and gene-level CNVs in CSF.

Ask AI

Helpful

Bookmark

View Full Paper