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

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

Authors:	Hickman, R. A.; Miller, A. M.; Holle, B. M.; Jee, J.; Liu, S. Y.; Ross, D.; Yu, H.; Riely, G. J.; Ombres, C.; Gewirtz, A. N.; Reiner, A. S.; Nandakumar, S.; Price, A.; Kaley, T. J.; Graham, M. S.; Vanderbilt, C.; Rana, S.; Hill, K.; Chabot, K.; Campos, C.; Nafa, K.; Shukla, N.; Karajannis, M.; Li, B.; Berger, M.; Ladanyi, M.; Pentsova, E.; Boire, A.; Brannon, A. R.; Bale, T.; Mellinghoff, I. K.; Arcila, M. E.
Article Title:	Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors
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-IMPACTTM) 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. © The Author(s) 2024.
Keywords:	adolescent; adult; child; aged; aged, 80 and over; middle aged; young adult; genetics; tumor marker; central nervous system tumor; central nervous system neoplasms; blood; cerebrospinal fluid; high throughput sequencing; high-throughput nucleotide sequencing; very elderly; humans; human; male; female; circulating tumor dna; biomarkers, tumor
Journal Title:	Acta Neuropathologica Communications
Volume:	12
ISSN:	2051-5960
Publisher:	BioMed Central Ltd.
Date Published:	2024-09-17
Start Page:	151
Language:	English
DOI:	10.1186/s40478-024-01846-4
PUBMED:	39289779
PROVIDER:	scopus
PMCID:	PMC11406943
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85204238543&doi=10.1186%2fs40478-024-01846-4&partnerID=40&md5=8a488381af865f896c1674c85a243578
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Ingo Mellinghoff and Maria Arcila -- Source: Scopus