Table 1.
Milestones in medulloblastoma diagnostics, research, and treatment.
| Year | Author | Probe | Method | Tumor | Milestone |
|---|---|---|---|---|---|
| 1910 | Wright [8] | Tumor (Autopsy and Biopsy/ Operation) |
Histology | Neurocytoma or neuroblastoma (before the creation of the term for medulloblastoma) |
A pathologist described CNS tumors differing from most others, later named medulloblastoma. Described as (pseudo-) rosettes, until today referred to as “Homer-Wright” rosettes. |
| 1925 | Cushing and Bailey [5] | Neurosurgically removed posterior fossa tumors | Histology | Medulloblastoma | Introduced the term medulloblastoma |
| 1953 | Paterson and Farr [9] | Clinical study | Irradiation: 5000 cGy posterior fossa 3500 cGy neuraxis |
Reached 65% 3-year survival of medulloblastoma | Irradiation treatment of the whole CNS |
| 1969 | Chang et al. [10] | Clinical study | Staging | Medulloblastoma | Staging system |
| 1973 | Hart and Earle [11] | Classification | Histology | PNET | Introduced term PNET, regardless of location within CNS |
| (1950-)1980s | Various authors [12] | Experimental and clinical studies | Development of different chemotherapies and combinations thereof | Brain tumors, incl. medulloblastoma | Introduction of antineoplastic agents for different types of cell cycle, incl. alkylating agents |
| 1991 | Eibl and Wiestler [13,14] | Experimentally induced tumors and derived cell lines | Retrovirus-mediated gene transfer of SV40 LT into neural transplants | PNET (indistinguishable from medulloblastoma morphology) |
Rat tumor model, histologically identical to human medulloblastoma (neuroblastic rosettes, bipotential differentiation), triggered medulloblastoma research in Bonn and Heidelberg, Germany |
| 1991 | Ohgaki, Eibl et al. [1] | Primary tumor tissue | SSCP-PCR, direct sequencing |
Medulloblastoma | First detection of p53 mutations in primary medulloblastoma tissue by Eibl, supporting Eibl’s earlier tumor model of the inactivation of p53, also triggered medulloblastoma research, incl. molecular profiling leading to current WHO classification |
| 2001 | Reya et al. [15] | Cancer stem cell (CSC) | Compared self-renewal of hematopoetic stem cells with heterogeneity of cancer cells | Migratory cancer stem cells | Established CSC theory (Weissman/Clarke) |
| 2014 | Bettegowda et al. [16] | ctDNA | Digital PCR, sequencing | 14 tumor types, incl. medulloblastoma | ctDNA detectable for most tumors outside the brain |
| 2016 | Louis et al. [2] | Tissue biopsy | Molecular genetics | Medulloblastoma | WHO classification introduced four medulloblastoma groups based on molecular profile (transcriptome) |
| 2018 | Garzia et al. [17] | CTC | Parabiotic xenograft model | Medulloblastoma | Hematogenous spread of metastasis to leptomeninges by chemokine-chemokine receptor |
| 2021 | Louis et al. [3] | Tissue biopsy | Molecular profile, incl. methylation profile | Medulloblastoma | WHO introduced methylome to further classify medulloblastoma groups |
| 2022 | Smith et al. [18] | Normal and tumor tissue | Multi-omics, molecular signatures, expression profiles | Medulloblastoma, groups 3 and 4 | Identification of “Cell of origin” in groups 3 and 4 derived from rhombic lip nodulus in developing cerebellum |
| 2022 | Hendrikse et al. [19] | Transcriptomics, mutations upstream of CBFA: CBFA2T2, CBFA2T3, PRDM6, UTX, OTX2 | Medulloblastoma group 4 | Identification of medulloblastoma group 4 progenitor cells in rhombic lip |