Background/Objectives: The latest National Comprehensive Cancer Network (NCCN) Central Nervous System (CNS) Guidelines recommend utilizing next-generation sequencing (NGS) to enable comprehensive genomic profiling (CGP) as the preferred approach for molecular characterization of central nervous system (CNS) malignancies. CNS malignancies present distinct challenges due to the infeasibility of tissue-based testing for many patients and the restrictive nature of the blood–brain barrier (BBB) making plasma-based liquid biopsy an ineffective alternative. Recent advances in liquid biopsy have extended molecular testing beyond plasma to include cerebrospinal fluid (CSF), which serves as a valuable source for tumor-derived nucleic acids. Methods: The Belay Summit™ 2.0 is a high-throughput CGP assay capable of detecting multiple variant types, including single nucleotide variants (SNVs) and small insertion and deletions (Indels), copy number variations (CNVs), gene fusions, splice variants, and immunotherapy biomarkers such as microsatellite instability (MSI) and tumor mutational burden (TMB). This study details the analytical and clinical validation of Summit™ 2.0 to assess its technical performance and clinical sensitivity. Analytical validation was conducted using 68 specimens, demonstrating robust and reproducible detection of all variant types with 15 ng of CSF-derived total nucleic acid (tNA). Results: The analytical sensitivity of the Belay Summit™ 2.0 assay for SNVs and Indels was determined to be 96.7% with a 100% limit of detection (LoD) at a variant allele frequency of 0.3%. Clinical validity was evaluated across a cohort of 118 CSF specimens, including both primary and metastatic CNS tumors, demonstrating 96% sensitivity and 98% specificity. Conclusions: These findings support the use of the Belay Summit™ 2.0 assay for accurate and reproducible genomic profiling of CNS tumors using tumor-derived nucleic acids from CSF in patients for whom tissue-based testing is considered infeasible, unsafe, or not deemed by the prescribing physician to be clinically appropriate.
背景/目标：最新的美国国家综合癌症网络（NCCN）中枢神经系统（CNS）指南推荐采用新一代测序技术进行全面的基因组分析，作为中枢神经系统恶性肿瘤分子特征鉴定的首选方法。由于对许多患者而言基于组织的检测难以实施，且血脑屏障的限制性使得基于血浆的液体活检效果有限，中枢神经系统恶性肿瘤的诊断面临独特挑战。液体活检领域的最新进展已将分子检测从血浆扩展到脑脊液，脑脊液已成为肿瘤来源核酸的重要来源。方法：Belay Summit™ 2.0是一种高通量全面基因组分析检测方法，能够检测多种变异类型，包括单核苷酸变异和小片段插入缺失、拷贝数变异、基因融合、剪接变异以及免疫治疗生物标志物如微卫星不稳定性和肿瘤突变负荷。本研究详细介绍了Summit™ 2.0的分析与临床验证过程，以评估其技术性能和临床灵敏度。使用68份样本进行验证分析，结果显示在15 ng脑脊液来源总核酸条件下，所有变异类型的检测均具有稳健性和可重复性。结果：Belay Summit™ 2.0检测对单核苷酸变异和小片段插入缺失的分析灵敏度为96.7%，在等位基因频率为0.3%时的检测限达到100%。在118份脑脊液样本（包括原发性和转移性中枢神经系统肿瘤）队列中评估临床有效性，结果显示灵敏度为96%，特异性为98%。结论：这些研究结果支持使用Belay Summit™ 2.0检测方法，通过脑脊液中的肿瘤来源核酸对中枢神经系统肿瘤进行准确、可重复的基因组分析，适用于那些基于组织的检测被认为不可行、不安全或经临床医生判断不适合的患者。
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