Which molecular marker is most commonly associated with medulloblastoma and is used for prognostic stratification?

Explanation

## Medulloblastoma — Molecular Subtypes and Prognostic Markers **Key Point:** Medulloblastoma is now classified into **four molecular subgroups** (WNT, SHH, Group 3, Group 4), each with distinct molecular signatures and prognostic implications. **WNT pathway activation with TP53 wild-type** defines the **WNT subgroup**, which carries the **most favorable prognosis**. ### Medulloblastoma Molecular Subtypes | Subtype | Key Markers | Prognosis | Frequency | |---------|-------------|-----------|----------| | **WNT** | β-catenin/CTNNB1 mutation, TP53 WT | **Excellent** (>90% 5-yr survival) | 10–15% | | **SHH** | PTCH1/SMO/SUFU mutation, TP53 mut/WT | Intermediate | 25–30% | | **Group 3** | MYC amplification, TP53 WT | **Poor** | 25–30% | | **Group 4** | MYCN amplification, TP53 WT | Poor | 35–40% | **High-Yield:** The **WNT subtype** is defined by **activating mutations in the WNT/β-catenin pathway** (especially CTNNB1) **combined with wild-type TP53**. This combination is strongly protective and is the single best prognostic marker for favorable outcome. ### Clinical Significance 1. **WNT subtype** tumors are typically **non-metastatic** at diagnosis and respond well to standard chemotherapy and radiation. 2. **SHH subtype** with **TP53 mutation** (Li-Fraumeni syndrome) has worse prognosis than SHH with TP53 wild-type. 3. **Group 3 and 4** (non-WNT, non-SHH) are associated with **MYC/MYCN amplification** and carry the poorest prognosis. **Clinical Pearl:** Molecular subgrouping now guides **de-escalation** of therapy in WNT tumors (reduced radiation dose) and **intensification** in Group 3/4 tumors. **Mnemonic:** **WNT = WIN** — WNT pathway activation = Winning prognosis (best survival).