来自中枢神经系统肿瘤患者的脑脊液中循环肿瘤DNA的现实世界经验
Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors
影响因子:5.70000
分区:医学1区 Top / 神经科学1区
发表日期:2024 Sep 17
作者:
Richard A Hickman, Alexandra M Miller, Bridget M Holle, Justin Jee, Si-Yang Liu, Dara Ross, Helena Yu, Gregory J Riely, Christina Ombres, Alexandra N Gewirtz, Anne S Reiner, Subhiksha Nandakumar, Adam Price, Thomas J Kaley, Maya S Graham, Chad Vanderbilt, Satshil Rana, Katherine Hill, Kiana Chabot, Carl Campos, Khedoudja Nafa, Neerav Shukla, Matthias Karajannis, Bob Li, Michael Berger, Marc Ladanyi, Elena Pentsova, Adrienne Boire, A Rose Brannon, Tejus Bale, Ingo K Mellinghoff, Maria E Arcila
摘要
肿瘤样本中遗传改变的表征已成为许多人类癌症实现更精确疾病分类并指导目标疗法的标准实践。脑脊液（CSF）可以作为中枢神经系统（CNS）癌症患者的肿瘤DNA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CSF循环肿瘤DNA（CTDNA）进行了全面分析。我们确定了具有临床记录的中枢神经系统肿瘤的489/922（53.0％）CSF样品的遗传改变。没有中枢神经系统肿瘤的患者的85个CSF样品中没有一个可检测到的CTDNA。临床上可作用的体细胞改变的分布与AACR精灵队列中肿瘤类型的特异性变化一致。来自相同患者的重复CSF CTDNA检查确定了克隆进化和抗性机制的出现。 CTDNA检测与CSF收集后的总生存期缩短有关。 CSF的下一代测序通过在常规医院环境中通过微创腰椎穿刺收集，在大量CNS肿瘤患者中提供了临床上可行的癌症基因型信息。
Abstract
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.