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Stratifying and Targeting Pediatric Medulloblastoma through Genomics

In this project, genomic analyses of pediatric medulloblastoma samples, obtained through the international medulloblastoma consortium, will be performed. RNA and miRNA expression profiles of 1000 samples, representing all four subgroups (Wnt, Shh, Group C, and D), will be studied to identify novel subtypes within each subgroup. The resulting subtype-specific expression profiles will support the development of reliable and robust biomarkers to more accurately and reliably classify medulloblastomas for treatment in clinical trials. For that purpose, two assays will be developed: an antibody-based immunohistochemical assay and an orthogonal nucleic acid-based hybridization assay. Additional genomic DNA analysis of the 300 high risk subgroup cases will support the discovery of subgroup specific somatic mutations in order to inform current clinical trials of targeted therapies, and to identify genes and pathways already targeted in other diseases. Such therapies could be rapidly transitioned to Phase II trials in medulloblastoma. Furthermore, the discovery of somatic mutations could be used for developing as well as validating specific biomarkers. The project team will also try to identify risk factors that predispose children to this type of cancer.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001000158 23
EGAD00001000723 42
EGAD00001000818 4
EGAD00001000946 125
EGAD00001001210 28
EGAD00001001461 30
EGAD00001001899 102
EGAD00001003907 79
EGAD00001004435 Illumina HiSeq 2000 145
EGAD00001004958 Illumina HiSeq 2000 Illumina HiSeq 2500 234
EGAD00001006305 Illumina HiSeq 2000 Illumina HiSeq 2500 82
EGAD00001008458 Illumina HiSeq 2000 Illumina HiSeq 2500 391
Publications Citations
Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
Nature 488: 2012 49-56
Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma.
Cancer Cell 26: 2014 33-47
Divergent clonal selection dominates medulloblastoma at recurrence.
Nature 529: 2016 351-357
HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma.
Cancer Cell 29: 2016 311-323
Medulloblastoma-associated DDX3 variant selectively alters the translational response to stress.
Oncotarget 7: 2016 28169-28182
Spatial heterogeneity in medulloblastoma.
Nat Genet 49: 2017 780-788
Pyruvate Kinase Inhibits Proliferation during Postnatal Cerebellar Neurogenesis and Suppresses Medulloblastoma Formation.
Cancer Res 77: 2017 3217-3230
Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.
Cancer Cell 32: 2017 295-309.e12
A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.
Cell 172: 2018 1050-1062.e14
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Acta Neuropathol Commun 6: 2018 48
p53 Function Is Compromised by Inhibitor 2 of Phosphatase 2A in Sonic Hedgehog Medulloblastoma.
Mol Cancer Res 17: 2019 186-198
Childhood cerebellar tumours mirror conserved fetal transcriptional programs.
Nature 572: 2019 67-73
Upregulation of the chromatin remodeler HELLS is mediated by YAP1 in Sonic Hedgehog Medulloblastoma.
Sci Rep 9: 2019 13611
Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.
Nature 574: 2019 707-711
Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma.
Nat Neurosci 23: 2020 842-853
A transcriptome-based classifier to determine molecular subtypes in medulloblastoma.
PLoS Comput Biol 16: 2020 e1008263
The transcriptional landscape of Shh medulloblastoma.
Nat Commun 12: 2021 1749
Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse.
Neuro Oncol 24: 2022 153-165
Subgroup and subtype-specific outcomes in adult medulloblastoma.
Acta Neuropathol 142: 2021 859-871
Failure of human rhombic lip differentiation underlies medulloblastoma formation.
Nature 609: 2022 1021-1028
The LIN28B-let-7-PBK pathway is essential for group 3 medulloblastoma tumor growth and survival.
Mol Oncol 17: 2023 1784-1802
MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma.
J Exp Clin Cancer Res 42: 2023 214
Heterogeneity and tumoral origin of medulloblastoma in the single-cell era.
Oncogene 43: 2024 839-850