Original Paper

Acta Neuropathologica

, Volume 123, Issue 4, pp 473-484

Open Access This content is freely available online to anyone, anywhere at any time.

Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas

  • Marcel KoolAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) Email author 
  • , Andrey KorshunovAffiliated withClinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ)
  • , Marc RemkeAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Pediatric Hematology and Oncology, Heidelberg University Hospital
  • , David T. W. JonesAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)
  • , Maria SchlansteinAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)
  • , Paul A. NorthcottAffiliated withArthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto
  • , Yoon-Jae ChoAffiliated withStanford University School of Medicine, Department of Neurology and Neurological Sciences
  • , Jan KosterAffiliated withDepartment of Oncogenomis, Academic Medical Center
  • , Antoinette Schouten-van MeeterenAffiliated withDepartment of Pediatric Oncology, Academic Medical Center
    • , Dannis van VuurdenAffiliated withDepartment of Pediatric Oncology/Hematology, Neuro-Oncology Research Group, Cancer Center Amsterdam, VU University Medical Center
    • , Steven C. CliffordAffiliated withNorthern Institute for Cancer Research, Newcastle University
    • , Torsten PietschAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Neuropathology, Bonn University
    • , Andre O. von BuerenAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf
    • , Stefan RutkowskiAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf
    • , Martin McCabeAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Manchester Academic Health Science CentreDepartment of Pathology, University of Cambridge
    • , V. Peter CollinsAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Pathology, University of Cambridge
    • , Magnus L. BäcklundAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Oncology-Pathology, Karolinska Institute, Karolinska University Hospital
    • , Christine HaberlerAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Neuropathology, Medical University
    • , Franck BourdeautAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Laboratoire de génétique et biologie des cancers, Institut Curie
    • , Olivier DelattreAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Laboratoire de génétique et biologie des cancers, Institut Curie
    • , Francois DozAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Pediatric Oncology, Institut Curie and University Paris Descartes
    • , David W. EllisonAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Pathology, St. Jude Children’s Research Hospital
    • , Richard J. GilbertsonAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Developmental Neurobiology, St. Jude Children’s Research Hospital
    • , Scott L. PomeroyAffiliated withClinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ)Department of Neurology, Children’s Hospital Boston, Harvard Medical School
    • , Michael D. TaylorAffiliated withClinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ)Arthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of TorontoDivision of Neurosurgery, Hospital for Sick Children, University of Toronto
    • , Peter LichterAffiliated withClinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ)Division of Molecular Genetics, German Cancer Research Center (DKFZ)
    • , Stefan M. PfisterAffiliated withDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ)Department of Pediatric Hematology and Oncology, Heidelberg University Hospital

Abstract

Medulloblastoma is the most common malignant brain tumor in childhood. Molecular studies from several groups around the world demonstrated that medulloblastoma is not one disease but comprises a collection of distinct molecular subgroups. However, all these studies reported on different numbers of subgroups. The current consensus is that there are only four core subgroups, which should be termed WNT, SHH, Group 3 and Group 4. Based on this, we performed a meta-analysis of all molecular and clinical data of 550 medulloblastomas brought together from seven independent studies. All cases were analyzed by gene expression profiling and for most cases SNP or array-CGH data were available. Data are presented for all medulloblastomas together and for each subgroup separately. For validation purposes, we compared the results of this meta-analysis with another large medulloblastoma cohort (n = 402) for which subgroup information was obtained by immunohistochemistry. Results from both cohorts are highly similar and show how distinct the molecular subtypes are with respect to their transcriptome, DNA copy-number aberrations, demographics, and survival. Results from these analyses will form the basis for prospective multi-center studies and will have an impact on how the different subgroups of medulloblastoma will be treated in the future.

Keywords

Medulloblastoma Pediatric brain tumor Subgroups Meta-analysis