Researchers identify molecular subtypes of pediatric brain tumor, paving way for treatment

A schematic diagram showing seven distinct molecular subtypes of medulloblastoma, a rare pediatric brain tumor / Courtesy of Kookmin University

A Kookmin University research team has identified previously unrecognized molecular subtypes of medulloblastoma, a rare and aggressive pediatric brain tumor, in collaboration with researchers in Korea and abroad, opening new possibilities for personalized treatment.

The university said Friday that the team, led by applied chemistry professor Kim Kyung-hee, conducted the study as part of the National Cancer Center’s Cancer Proteogenomics Research Program, an initiative dedicated to advancing proteogenomics-based precision medicine for cancer.

The collaborative research team included Kim Young-wook of the National Cancer Center, Park Jong-bae of Kyung Hee University, Kim Seung-ki of Seoul National University, Yoon Jong-hyuck of the Korea Brain Research Institute and Jason K. Sa of Korea University.

International collaborators included Antonio Iavarone and Fulvio D’Angelo from the University of Miami Miller School of Medicine and Michael D. Taylor of the Toronto-based Hospital for Sick Children.

The researchers performed a comprehensive proteogenomic analysis by integrating genomic, transcriptomic, epigenomic (DNA methylome), proteomic and phosphoproteomic data from tumor samples collected from more than 100 patients with medulloblastoma.

Based on the integrated analysis, the researchers refined the conventional four molecular groups of medulloblastoma — WNT, SHH, Group 3 and Group 4 — into seven distinct molecular subtypes.

They also subdivided the SHH group into SHHα and SHHβ, and Group 4 into G4α, G4β and G4γ, revealing that the refined classification more accurately captures the biological characteristics of the tumors and predicts their clinical outcomes.

The study found that the SHHβ and G4γ subtypes exhibited enhanced neuronal differentiation and were associated with relatively favorable clinical outcomes.

In contrast, the SHHα, G4α and G4β subtypes were linked to a higher risk of disease recurrence and progression.

The researchers also identified subtype-specific protein signaling pathways and uncovered potential therapeutic targets for each molecular subtype, highlighting new opportunities for precision medicine-based targeted therapies.

Kim Kyung-hee, an applied chemistry professor at Kookmin University / Courtesy of Kookmin University

The findings were published last month in the peer-reviewed medical journal Experimental & Molecular Medicine under the title “Comprehensive proteogenomic characterization reveals clinically relevant molecular subtypes associated with medulloblastoma progression.”

“Our integrated analysis of cancer proteogenomic data, which captures the functional characteristics of tumors, has enabled us to develop a more refined classification system that provides a deeper understanding of the molecular diversity of medulloblastoma,” said professor Kim of Kookmin University.

She added, “We expect these findings to serve as an important foundation for developing personalized treatment strategies and subtype-specific targeted therapies in the future.”

Medulloblastoma is the most common malignant brain tumor in children, and the current standard of care consists of surgical resection followed by radiation therapy and chemotherapy.

However, substantial molecular heterogeneity among patients results in marked differences in treatment response and clinical outcomes.

Survival rates following tumor recurrence remain poor after disease recurrence, underscoring the need for precision medicine approaches based on the molecular characteristics of individual tumors.