肿瘤样本中基因改变的表征已成为许多人类癌症的标准做法，以实现更精确的疾病分类并指导靶向治疗的选择。脑脊液 (CSF) 可作为中枢神经系统 (CNS) 癌症患者肿瘤 DNA 的来源。我们在医院实验室使用 FDA 授权的平台 (MSK-IMPACT™) 对 711 名患者的脑脊液循环肿瘤 DNA (ctDNA) 进行了全面分析。我们在 489/922 (53.0%) 份具有临床记录的中枢神经系统肿瘤的脑脊液样本中发现了基因改变。来自非中枢神经系统肿瘤患者的 85 份脑脊液样本均未检测到 ctDNA。 AACR GENIE 队列中临床上可操作的体细胞改变的分布与肿瘤类型特异性改变一致。对同一患者的重复脑脊液 ctDNA 检查确定了克隆进化和耐药机制的出现。 ctDNA 检测与脑脊液采集后总生存期缩短有关。在常规医院环境中通过微创腰椎穿刺收集的新一代脑脊液测序可为大部分中枢神经系统肿瘤患者提供临床上可行的癌症基因型信息。© 2024。作者。

The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.© 2024. The Author(s).