Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult

Adult brainstem gliomas are rare and present unique diagnostic and therapeutic challenges due to their critical location and limited biopsy feasibility. Molecular profiling of tumor-derived DNA (t-DNA) isolated from cerebrospinal fluid (CSF) is emerging as a minimally invasive alternative for charac...

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Main Authors: Michael Youssef, Alexandra Larson, Vindhya Udhane, Kala F. Schilter, Qian Nie, Honey V. Reddi
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:The Journal of Liquid Biopsy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950195425000347
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author Michael Youssef
Alexandra Larson
Vindhya Udhane
Kala F. Schilter
Qian Nie
Honey V. Reddi
author_facet Michael Youssef
Alexandra Larson
Vindhya Udhane
Kala F. Schilter
Qian Nie
Honey V. Reddi
author_sort Michael Youssef
collection DOAJ
description Adult brainstem gliomas are rare and present unique diagnostic and therapeutic challenges due to their critical location and limited biopsy feasibility. Molecular profiling of tumor-derived DNA (t-DNA) isolated from cerebrospinal fluid (CSF) is emerging as a minimally invasive alternative for characterizing these tumors and guiding targeted therapy. A 34-year-old woman with brainstem glioma was treated with a standard course of radiation and temozolomide (TMZ) and remained stable for several years. After surveillance imaging revealed disease progression and raised suspicion of IDH-mutant disease on MRI spectroscopy, molecular profiling of CSF was ordered. The Belay Summit test, a novel NGS-based liquid biopsy assay for central nervous system (CNS) tumors, identified variants in IDH1 and TP53 as well as loss of CDKN2A/CDKN2B. Based on these findings, the patient received a short course of radiation and was started on the IDH inhibitor vorasidenib. This case demonstrates the use of t-DNA from CSF for molecular profiling of adult brainstem glioma to identify actionable genomic alterations without surgical risk and allow patients to receive targeted therapy without tissue diagnosis.
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spelling doaj-art-1c4fb37229bb453b9c6d71e5581d45df2025-08-20T03:58:21ZengElsevierThe Journal of Liquid Biopsy2950-19542025-09-01910031810.1016/j.jlb.2025.100318Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adultMichael Youssef0Alexandra Larson1Vindhya Udhane2Kala F. Schilter3Qian Nie4Honey V. Reddi5Department of Neurology and the Department of Hematology and Oncology at UT Southwestern Medical Center, Dallas, TX 75235, USABelay Diagnostics, Chicago, IL, 60607, USABelay Diagnostics, Chicago, IL, 60607, USABelay Diagnostics, Chicago, IL, 60607, USABelay Diagnostics, Chicago, IL, 60607, USABelay Diagnostics, Chicago, IL, 60607, USA; Corresponding author. 1375 W Fulton St, Suite 530, Chicago, IL 60607, USA.Adult brainstem gliomas are rare and present unique diagnostic and therapeutic challenges due to their critical location and limited biopsy feasibility. Molecular profiling of tumor-derived DNA (t-DNA) isolated from cerebrospinal fluid (CSF) is emerging as a minimally invasive alternative for characterizing these tumors and guiding targeted therapy. A 34-year-old woman with brainstem glioma was treated with a standard course of radiation and temozolomide (TMZ) and remained stable for several years. After surveillance imaging revealed disease progression and raised suspicion of IDH-mutant disease on MRI spectroscopy, molecular profiling of CSF was ordered. The Belay Summit test, a novel NGS-based liquid biopsy assay for central nervous system (CNS) tumors, identified variants in IDH1 and TP53 as well as loss of CDKN2A/CDKN2B. Based on these findings, the patient received a short course of radiation and was started on the IDH inhibitor vorasidenib. This case demonstrates the use of t-DNA from CSF for molecular profiling of adult brainstem glioma to identify actionable genomic alterations without surgical risk and allow patients to receive targeted therapy without tissue diagnosis.http://www.sciencedirect.com/science/article/pii/S2950195425000347Brainstem gliomaIDH-MutationGenomic testingCSFLiquid biopsy
spellingShingle Michael Youssef
Alexandra Larson
Vindhya Udhane
Kala F. Schilter
Qian Nie
Honey V. Reddi
Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult
The Journal of Liquid Biopsy
Brainstem glioma
IDH-Mutation
Genomic testing
CSF
Liquid biopsy
title Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult
title_full Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult
title_fullStr Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult
title_full_unstemmed Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult
title_short Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult
title_sort analysis of cerebrospinal fluid tumor derived dna to obviate biopsy of idh mutant brainstem glioma in an adult
topic Brainstem glioma
IDH-Mutation
Genomic testing
CSF
Liquid biopsy
url http://www.sciencedirect.com/science/article/pii/S2950195425000347
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