Molecular subtypes of medulloblastoma

Multiple medulloblastoma subtypes have been identified by integrative molecular analysis.[92-115] Since 2012, the general consensus is that medulloblastoma can be molecularly separated into at least four core subtypes, including WNT-activated, sonic hedgehog (SHH)–activated, group 3, and group 4. In the 2021 World Health Organization (WHO) classification, the SHH subgroup has been divided into two groups based on TP53 status. Group 3 and group 4, which require methylation analysis for reliable separation, have been combined into medulloblastoma, non-WNT/non-SHH. Because the group 3 and group 4 terminology has been used extensively in completed studies and is still in use in ongoing and planned studies, this nomenclature will be maintained throughout the clinical discussion in this summary.[1,78]

Different regions of the same tumor are likely to have other disparate genetic variants, adding to the complexity of devising effective molecularly targeted therapy.[110] However, the major subtypes noted above remain stable across primary and metastatic components.[111,114]

Further subclassification within these subgroups is possible, which will provide even more prognostic information.[112-114]