Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Nature. 2012 Aug 2;488(7409):49-56. doi: 10.1038/nature11327.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Cerebellar Neoplasms / classification*
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / metabolism
  • Child
  • DNA Copy Number Variations / genetics
  • Gene Duplication / genetics
  • Genes, myc / genetics
  • Genome, Human / genetics*
  • Genomic Structural Variation / genetics*
  • Genomics
  • Hedgehog Proteins / metabolism
  • Humans
  • Medulloblastoma / classification*
  • Medulloblastoma / genetics*
  • Medulloblastoma / metabolism
  • NF-kappa B / metabolism
  • Nerve Tissue Proteins / genetics
  • Oncogene Proteins, Fusion / genetics
  • Proteins / genetics
  • RNA, Long Noncoding
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Translocation, Genetic / genetics


  • Carrier Proteins
  • Hedgehog Proteins
  • NF-kappa B
  • Nerve Tissue Proteins
  • Oncogene Proteins, Fusion
  • PVT1 long-non-coding RNA, human
  • Proteins
  • RNA, Long Noncoding
  • SHH protein, human
  • SNCAIP protein, human
  • Transforming Growth Factor beta

Associated data

  • GEO/GSE37385