Related Experiment Video
Updated: Jun 13, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Tumor extracellular vesicle RNA profiling predicts treatment response in pediatric diffuse midline glioma
Changheon Kim1, Junbeom Kim1, Sunjong Ji2,3
1Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Abstract:
Detection of reliable markers of therapy response and drug resistance remains a major unmet need in brain cancer, as serial tumor biopsy is often not feasible. This challenge is particularly acute in diffuse midline glioma (DMG), a fatal pediatric brain tumor for which new targeted therapies are entering clinical use, yet tools for real-time molecular analysis of tumor evolution during therapy remain lacking. Here, we demonstrate that plasma tumor-derived extracellular vesicle (EV) profiling provides a minimally invasive and complementary approach for diagnosis and longitudinal molecular monitoring in H3K27M-mutant DMG. Across patient-derived tumor models and clinical plasma samples, EV mRNA levels correlated strongly with parental tumor transcriptomes. EV H3K27M mRNA enabled discrimination of DMG from non-DMG controls, and exploratory EV response-associated mRNAs were linked to radiographic response and progression-free survival in patients receiving ONC201. To enable tumor-selective EV enrichment and multiplexed molecular profiling within a clinically practical workflow, we developed a new integrated platform supporting same-day EV analysis from small plasma volumes. This work represents the first proof-of-concept demonstration of the diagnostic and treatment response relevance of tumor-derived EV RNA in pediatric DMG and establishes a generalizable framework for minimally invasive longitudinal molecular monitoring in diseases where tissue access is inherently limited.
Insights
Plasma extracellular vesicle (EV) profiling offers a minimally invasive method for diagnosing diffuse midline glioma (DMG) and monitoring treatment response. This approach tracks tumor evolution through EV RNA, aiding in the development of targeted therapies for pediatric brain cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Reliable markers for therapy response and drug resistance in brain tumors are crucial but difficult to obtain due to the infeasibility of serial tumor biopsies.
- This challenge is especially significant in diffuse midline glioma (DMG), a pediatric brain tumor with limited molecular monitoring tools during targeted therapy.
- Current diagnostic and monitoring methods for DMG lack the real-time molecular analysis needed to track tumor evolution during treatment.
Purpose of the Study:
- To investigate plasma tumor-derived extracellular vesicle (EV) profiling as a minimally invasive method for diagnosing H3K27M-mutant DMG.
- To establish the utility of EV profiling for longitudinal molecular monitoring of tumor evolution during therapy.
- To develop and validate a practical workflow for EV enrichment and multiplexed molecular profiling.
Main Methods:
- Analysis of extracellular vesicles (EVs) isolated from plasma samples of patients with H3K27M-mutant DMG and controls.
- Correlation of EV mRNA levels with parental tumor transcriptomes using patient-derived tumor models and clinical samples.
- Development of an integrated platform for same-day EV analysis, including tumor-selective EV enrichment and multiplexed molecular profiling.
Main Results:
- Plasma EV mRNA levels showed a strong correlation with tumor transcriptomes, validating EV profiling as a reflection of tumor molecular state.
- EV H3K27M mRNA successfully differentiated DMG patients from non-DMG controls, indicating diagnostic potential.
- Exploratory analysis revealed that EV response-associated mRNAs correlated with radiographic response and progression-free survival in patients treated with ONC201.
Conclusions:
- Plasma EV profiling is a feasible and minimally invasive approach for the diagnosis of H3K27M-mutant DMG.
- EV RNA analysis provides valuable insights into tumor molecular evolution and can serve as a biomarker for treatment response.
- The developed integrated platform enables practical, same-day EV analysis, establishing a framework for longitudinal molecular monitoring in challenging-to-biopsy diseases like pediatric DMG.
Related Concept Videos
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...