Are molecular subgroups of medulloblastomas really prognostic?

Area of Science:

• Pediatric Oncology
• Molecular Biology
• Genetics

Background:

• Medulloblastoma classification has evolved beyond clinical and biologic criteria.
• Previous consensus identified four molecular groups, with recent updates providing further refinement.

Purpose of the Study:

• To review recent molecular classifications of medulloblastoma.
• To discuss how these classifications impact clinical trial design and therapeutic strategies.

Main Methods:

• Review of recent scientific literature (2017 onwards) on medulloblastoma molecular classification.
• Analysis of pathway activation (wingless/WNT, sonic hedgehog/SHH) and patient age in defining subgroups.
• Identification of specific drivers for Group 3 and Group 4 medulloblastomas.

Main Results:

• Medulloblastoma is now classified into 12 molecular subgroups (e.g., WNT, SHH, Group 3, Group 4).
• Paediatric medulloblastoma comprises seven subgroups, including distinct infant SHH subtypes (iSHH-I vs. iSHH-II) with differing prognoses.
• Specific molecular drivers for Group 3 and Group 4 have been identified.

Conclusions:

• Molecular classification challenges the traditional view of medulloblastoma as a single disease.
• Refined classifications enable tailored clinical trial designs, stratifying patients for risk-adapted therapies.
• Low-risk medulloblastoma patients may receive less toxic treatments, while high-risk patients could benefit from targeted therapies.