A 5-year-old child presents with a midline cerebellar mass. Histology shows small round blue cells with Homer Wright rosettes, high mitotic rate, and necrosis. Molecular testing shows activation of the Sonic Hedgehog (SHH) pathway. Which translocation or genetic alteration is most commonly associated with this tumor subtype?

• A t(11;22)(q24;q12) EWSR1-FLI1 fusion
• B Loss of chromosome 13q (PTCH1 mutations) ✓
• C Isochromosome 17q
• D IDH1 R132H mutation

Explanation

Medulloblastoma, SHH-activated subtype, is characterized by mutations in the SHH pathway, most commonly PTCH1 loss-of-function mutations on chromosome 9q22.3 or SUFU mutations. PTCH1 is on chromosome 9, but the key concept is SHH pathway activation. Isochromosome 17q is seen in medulloblastoma but is more characteristic of group 3/group 4. t(11;22) is seen in Ewing sarcoma/peripheral PNET. IDH1 mutations are seen in adult diffuse gliomas, not medulloblastomas.

Reference: WHO Classification of Tumours of the Central Nervous System, 5th (2021) ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.