Demography, clinical and molecular characteristics of MB
| Subgroup | WNT | SHH | Non-WNT/non-SHH group 3 | Non-WNT/non-SHH group 4 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subtype | WNT | WNT | SHH | SHH | SHH | SHH | Group | Group | Group | Group | Group | Group | |
| α | β | α | β | γ | δ | 3α | 3β | 3γ | 4α | 4β | 4γ | ||
| Demography and clinical features | Age at diagnosis (years, median) | 10 | 20 | 8 | 1.9 | 1.33 | 26 | 4.82 | 7.55 | 5 | 8.22 | 10 | 7 |
| Subtype proportion (%) | 70 | 30 | 29.1 | 15.7 | 21.1 | 34.1 | 46.5 | 25.7 | 27.8 | 30.1 | 33.4 | 36.5 | |
| Metastases (%) | 8.6 | 21.4 | 20 | 33 | 8.9 | 9.4 | 43.4 | 20 | 39.4 | 40 | 40.7 | 38.7 | |
| Survival rate (5 years, %) | 97 | 100 | 69.8 | 67.3 | 88 | 88.5 | 66.2 | 55.8 | 41.9 | 66.8 | 75.4 | 82.5 | |
| Molecular features | Gene mutation | CTNNB1, TP53, DDX3X, MLL2/3 | PTCH1, SMO, SUFU, TP53, DDX3X, CREBBP, MLL2/3, TERT, KDM6A | TERT, KDM6A | TERT, KDM6A | ||||||||
| Gene modification | TNRC6C methy | TNRC6C methy, MXI1 methy, IL8 methy | TNRC6C methy, MXI1 methy, IL8 methy | TNRC6C methy, MXI1 methy, IL8 methy, Lmx1A enhancer activation, PRDM6 induction | |||||||||
| Copy number variation | OTX2 amp, CDK6 amp | MYCN amp, CDK6 amp, PTEN loss, GLI2 amp | MYC amp, OTX2 amp, CDK6 amp, KDM6A loss, KBTBD4 insertion | MYCN amp, OTX2 amp, CDK6 amp, PTEN loss, KDM6A loss, KBTBD4 insertion | |||||||||
| miRNA profile | miR-183, miR-206 | miR-206 | miR-592, miR-182, miR-193a, miR-183, miR-206 | miR-592, miR-182, miR-183, miR-206 | |||||||||
| Other events | - | - | GFI1/GFI1B activation, MYC acetylation, and phosphorylation | GFI1/GFI1B activation, ERBB4-SRC activation | |||||||||
| Potential targeted drugs | WNT/β-catenin inhibitor | SMO inhibitor, GLI inhibitor, PI3K inhibitor, CDK4/6 inhibitor | CDK4/6 inhibitor, MYC inhibitor | CDK4/6 inhibitor | |||||||||
amp: amplification; CDK6: cyclin-dependent kinases 6; CREBBP: cAMP-response element binding protein (CREB)-binding protein; CTNNB1: cadherin-associated protein beta 1; DDX3X: DEAD-box helicase 3 X-linked; ERBB4-SRC: Erb-b2 receptor tyrosine kinase 4 (ERBB4)-proto-oncogene tyrosine-protein kinase SRC (SRC); GFI1: growth factor independent 1; GLI2: glioma-associated oncogene homolog 2; IL8: interleukin 8; KBTBD4: Kelch repeat and broad-complex, tramtrack, and bric-a-brac domain containing 4; KDM6A: lysine-specific demethylase 6A; Lmx1A: LIM homeobox transcription factor 1, alpha; methy: methylation; miRNA: microRNA; MLL2/3: mixed-lineage leukemia 2/3; MXI1: max interactor 1; MYC: myelocytomatosis oncogene; MYCN: neuroblastoma derived MYC; OTX2: orthodenticle homeobox 2; PI3K: phosphatidylinositol 3-kinase; PRDM6: PR/SET domain 6; PTCH1: patched 1; PTEN: phosphatase and tensin homolog; SMO: smoothened; SUFU: suppressor of fused; TERT: telomerase reverse transcriptase; TNRC6C: trinucleotide repeat containing 6C; -: blank cell