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.

IF 3.4 3区 医学 Q1 PATHOLOGY
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, Honey V Reddi
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引用次数: 0

Abstract

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 DNA-based genomic profiling of CSF to inform diagnosis of CNS tumors. The analytical sensitivity of Summit for single-nucleotide/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.

原发性和转移性中枢神经系统癌脑脊液DNA变异检测的分析验证和临床敏感性
与大多数实体瘤不同,由于血脑屏障的存在,中枢神经系统(CNS)的癌症对通过血浆进行有效检测和跟踪提出了独特的挑战。使用液体活检法评估脑脊液(CSF)中肿瘤来源的DNA,可以促进原发性和转移性中枢神经系统肿瘤的知情诊断,潜在地提高诊断的有效性,并减少与目前涉及神经外科手术的护理标准相关的不确定性和发病率。Belay Summit检测包括肿瘤来源的基于dna的脑脊液基因组分析,以告知中枢神经系统肿瘤的诊断。在0.30%变异等位基因分数的95%检测限下,Summit对单核苷酸/多核苷酸变异和插入/缺失的分析灵敏度为96%。染色体臂水平非整倍体在abs(log2r) 0.09检测限时的分析灵敏度为91%。124个标本的临床敏感性,包括原发性和转移性中枢神经系统肿瘤,被证明为90%,特异性为95%,支持潜在的积极临床应用。这些结果表明,Belay Summit试验可以准确且可重复地用于脑脊液对原发性和转移性中枢神经系统肿瘤的诊断。
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来源期刊
CiteScore
8.10
自引率
2.40%
发文量
143
审稿时长
43 days
期刊介绍: The Journal of Molecular Diagnostics, the official publication of the Association for Molecular Pathology (AMP), co-owned by the American Society for Investigative Pathology (ASIP), seeks to publish high quality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine. The editors welcome for review articles that contain: novel discoveries or clinicopathologic correlations including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, clinical informatics, or the description of polymorphisms linked to disease states or normal variations; the application of diagnostic methodologies in clinical trials; or the development of new or improved molecular methods which may be applied to diagnosis or monitoring of disease or disease predisposition.
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