To perform a comprehensive analysis of various studies which have delved into the use of Liquid Biopsy (LB) for diagnostic/ prognostic applications in Diffuse Midline Glioma (DMG), to gather a strong knowledge base on its diagnostic/prognostic potential and postulate future promises.  

DMG is a high-grade paediatric brain tumor with extremely poor prognosis and a leading cause of brain tumor death in children. Due to the sensitive location of lesion and an intact blood-brain barrier, both surgical intervention and therapeutic delivery to the site are ineffective, often making palliative radiotherapy the only treatment option. Current diagnostic methods include imaging (MRI/CT), followed by stereotactic biopsy to confirm mutation in H3K27M gene.

LB is a simple procedure which overcomes the limitations of conventional biopsies- invasiveness, risk of infection and difficulty in repeated sampling. LB for DMG involves collection of blood, Cerebrospinal Fluid (CSF) or other bodily fluids to detect the presence of circulating tumor DNA (CtDNA) and similar tumor-associated products. These can be found at early stages and their levels are found to affect prognosis and disease burden.

Google Scholar, PubMed and Scopus were used to gather around 100 relevant references comprising of research studies, clinical reports, case studies, review articles and analyses published between 2015 and 2025, using the keywords “DMG” and “diagnostics”. They were saved in Mendeley Reference Manager. These studies were used to gather information for the analysis and draw necessary conclusions.

Plethora of previous studies indicate that analysis of cell-free DNA (cfDNA) from CSF delivers high sensitivity and renders helpful insights for DMG diagnosis when conventional biopsy is unfeasible.