Isocitrate Dehydrogenase Mutation Assessment in Human Glioma Using Desorption Electrospray Ionization-Multiple...

Area of Science:

• Neuro-oncology
• Analytical Chemistry
• Biomarker Discovery

Background:

• Isocitrate dehydrogenase (IDH) mutation status is crucial for glioma diagnosis and prognosis but is typically determined post-surgery.
• Intraoperative molecular diagnosis is vital for maximizing safe tumor resection by differentiating tumor from normal brain tissue.

Purpose of the Study:

• To develop and validate a rapid, intraoperative method for predicting IDH mutation status in glioma patients.
• To utilize 2-hydroxyglutarate (2HG) as a surrogate marker for IDH mutation using mass spectrometry.

Main Methods:

• Desorption electrospray ionization-multiple reaction monitoring (DESI-MRM), a mass spectrometry technique, was employed for rapid analysis.
• 30 human brain smears were analyzed to predict IDH mutation status and quantify 2HG.
• Nanoelectrospray ionization (nESI) was used for validation, and isotopically labeled standards enabled quantitative measurements.

Main Results:

• DESI-MRM accurately predicted IDH mutation status with 100% agreement with clinical diagnosis within minutes.
• 2HG concentrations were significantly higher in IDH-mutant samples (88-1445 ng mg-1) compared to IDH-wildtype samples (9-15 ng mg-1).
• The method demonstrated accuracy within ≤15% and a strong correlation between 2HG levels and IDH mutation status.

Conclusions:

• DESI-MRM is a standalone, rapid, and accurate method for intraoperative prediction of IDH mutation status in glioma.
• This technique supports surgical decision-making, potentially improving patient outcomes by enabling precise tumor resection.
• Quantification of 2HG via DESI-MRM offers a valuable tool for real-time molecular diagnostics in neuro-oncology.