Table 2.
Clinical and molecular characteristics of subgroups of medulloblastoma
| WNT (~10%) | SHH (~30%) | Group 3 (~25%) | Group 4 (~35%) | |
|---|---|---|---|---|
| Clinical | ||||
| Sex ratio | 1:1 | 1.5:1 | 2:1 | 3:1 |
| Age distribution | Older children | Infants, children, adults | Mostly infants | Older children and young adults |
| Histology | Classic; very rarely LCA | Classic >nodular/desmoplastic >LCA >MBEN | Classic >LCA | Classic; rarely LCA |
| Metastasis at diagnosis | 5%–10% | 15%–20% | 40%–45% | 35%–40% |
| Overall survival | ~95% | ~75% | ~50% | ~75% |
| Proposed cell of origin | Lower rhombic lip progenitor cells | CGNP of the EGL and cochlear nucleus | Prominin-1+, lineage− neural stem cells; CGNPs of the EGL | Unknown |
| Genomic | ||||
| Cytogenetic | 6− | 3q+ 9p+ 9q− 10q− 14q− 17p− | 1q+ 7+ 17q+ 18+ 8− 10q− 11− 16q− 17p− | 4+ 7+ 17q+ 18+ 8− 10− 11− 17p− X− |
| Driver genes |
CTNNB1 (90.6%) DDX3X (50%) SMARCA4 (26.3%) MLL2 (12.5%) TP53 (12.5%) |
PTCH1 (28%) TP53 (13.6%) MLL2 (12.9%) DDX3X (11.7%) MycN (8.2%) BCOR (8%) LDB1 (6.9%) TCF4 (5.5%) GLI2 (5.2%) |
Myc (16.7%) PVT1 (11.9%) SMARCA4 (10.5%) OTX2 (7.7%) CTDNEP1 (4.6%) LRP1B (4.6%) MLL2 (4%) |
KDM6A (13%) SNCAIP (10.4%) MycN (6.3%) MLL3 (5.3%) CDK6 (4.7%) ZMYM3 (3.7%) |
| Expression signature | WNT signaling | SHH signaling |
Myc signature Retinal signature |
Neuronal signature |
Note: Adapted with permission from Macmillan Publishers Limited: Nat Rev Cancer. Northcott PA, Jones DT, Kool M, et al. Medulloblastomics: the end of the beginning. Nat Rev Cancer. 2012;12:818–834.27 Copyright © 2012.
Abbreviations: WNT, wingless; SHH, Sonic Hedgehog; LCA, large cell/anaplastic; MBEN, medulloblastoma with excessive nodularity; CGNP, cerebellar granular neuron precursor; EGL, external granular layer.