ICGC PedBrainTumor

This page explains some highlights of the research we have carried out in the course of the PedBrainTumor project.



This type of brain tumor most common malignant brain tumour in children and can be subdivided in four distinct subgroups: WNT, SHH, Group 3 and Group 4 (Kool, M. et al. Acta Neuropathol. 123, 2012; Taylor, M. D. et al. Acta Neuropathol. 123, 2012).


In our studies we found (Jones et al. Nature, 488, 2012)

  • a high percentage of medulloblastomas – particularly in group 3 & 4 – possess four sets of chromosomes instead of two as normal (tetraploidy)
  • a positive correlation between patient age and mutation rate was observed
  • several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumor (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns
  • RNA sequencing confirmed these alterations, and revealed the finding of the first medulloblastoma fusion genes
  • Chromatin modifiers were frequently altered across all subgroups


In some medulloblastoma cases the so called phenomenon "chromothripsis" was observed, which is a catastrophic single event that leads to hundreds and thousands of chromosomal rearrangements (Rausch et al. Cell, 148, 2012). This event seems to occur in association with a germline TP53 mutation in SHH medulloblastoma. The same association has been observed in acute myeloid leukemia.


A large scale study of more than 1000 medulloblastoma genomes revealed a high number of structural aberrations (somatic copy number aberrations) which are common in distinct medulloblastoma subgroups. Some of these structural aberrations affect known pathways and might open up the possibility for rational, targeted therapy (Northcott et al. Nature, 488, 2012).


Pilocytic Astrocytoma - a single pathway disease

This is the most frequent type of brain tumor in children. Our studies revealed that all gene defects found in this type affect the MAPK signaling pathway. This finding may lead to new potential therapeutic targets. (Jones et al. Nature Genetics, 45, 2013)



The investigation into the molecular genetics of glioblastoma yielded new insights into this most malignant type of brain tumor. According to the molecular analyses six subgroups have been indentified in glioblastoma across all age groups. These findings may lead to novel treatment approaches in this malignant disease. (Sturm et al. Cancer Cell, 2012)
Two of these six glioblastoma subgroups have been previously identified by two distinct mutations which affect the histone gene H3.3. This gene is responsible for packaging the DNA into a coiled structure and has gene regulatory effects. (Schwartzentruber et al. Nature, 482, 2012)







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