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

Authors:

Michael Youssef, Alexandra Larson, Vindhya Udhane, Kala F. Schilter, Qian Nie, Honey V. Reddi

Journal:

The Journal of Liquid Biopsy, Volume 9100318, September 2025.

Abstract:

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.