中枢神经系统肿瘤患者循环肿瘤DNA在脑脊液中的临床应用经验

Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors

Acta Neuropathologica Communications

影响因子:5.7

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

DOI: 10.1186/s40478-024-01846-4

摘要

肿瘤样本中遗传变异的检测已成为许多肿瘤实现更精确疾病分类和指导靶向治疗的标准做法。脑脊液（CSF）可以作为中枢神经系统（CNS）癌症患者肿瘤DNA的来源。我们在一所医院的实验室中，使用FDA授权平台（MSK-IMPACT™）对711名患者的CSF循环肿瘤DNA（ctDNA）进行了全面检测。结果显示，在489/922（53.0%）具有临床记录的CNS肿瘤的CSF样本中检测到遗传变异。无CNS肿瘤的85个CSF样本中均未检测到ctDNA。具有临床指导意义的体细胞变异的分布与AACR GENIE队列中肿瘤类型特异性变异一致。同一患者多次采集的CSF ctDNA检测揭示了克隆演化和耐药机制的出现。ctDNA检测与采集后总体生存期缩短相关。在常规医院环境中，通过微创腰穿收集的CSF进行的下一代测序，为大量CNS肿瘤患者提供了具有临床指导意义的癌症基因型信息。

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.