Medulloblastoma molecular groups (WNT, SHH, group 3, group 4)

What is measured: the molecular group of the tumour. How: DNA methylation profiling (the Heidelberg classifier) is the reference; where it is unavailable, immunohistochemistry surrogates (nuclear beta-catenin for WNT; GAB1, YAP1 and filamin A for SHH) plus targeted sequencing (CTNNB1, PTCH1, SUFU, SMO, TP53) and FISH or copy-number for MYC and MYCN amplification and isochromosome 17q. WHO 2021 recognises WNT-activated, SHH-activated TP53-wild-type, SHH-activated TP53-mutant, and non-WNT/non-SHH (groups 3 and 4, further split into subgroups I to VIII). Metastatic staging by spinal MRI and cerebrospinal fluid cytology (Chang M0 to M4) and extent of resection sit alongside. What a result changes: WNT (about 10 percent, older children, near 95 percent survival) is the target of trials that cut the craniospinal dose; SHH splits by age and TP53, with infants treated on radiation-sparing chemotherapy, TP53-mutant SHH tumours (often germline Li-Fraumeni) carrying the worst outlook and upstream PTCH1 or SMO mutations making adult SHH tumours candidates for SMO inhibitors; group 3 with MYC amplification is high risk and gets intensified therapy, while group 4 with chromosome 11 loss or whole chromosome 17 gain is low risk and a de-escalation candidate. Where it matters: medulloblastoma and its WNT, SHH and group 3/4 pages; the same methylation approach subgroups ATRT (TYR, SHH, MYC) and ependymoma.