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Nature. 2012 488 (7409)
· PMCID: PMC3683624
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.
MeSH Terms (21)Carrier Proteins Cerebellar Neoplasms Child DNA Copy Number Variations Gene Duplication Genes, myc Genome, Human Genomics Genomics Genomic Structural Variation Hedgehog Proteins Humans Medulloblastoma Nerve Tissue Proteins NF-kappa B Oncogene Proteins, Fusion Proteins RNA, Long Noncoding Signal Transduction Transforming Growth Factor beta Translocation, Genetic