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 Kool, Andrey Korshunov, Marc Remke, David T.W. Jones, Maria Schlanstein, Paul A. Northcott, Yoon Jae Cho, Jan Koster, Antoinette Schouten-Van Meeteren, Dannis Van Vuurden, Steven C. Clifford, Torsten Pietsch, Andre O. Von Bueren, Stefan Rutkowski, Martin McCabe, V. Peter Collins, Magnus L. Bäcklund, Christine Haberler, Franck Bourdeaut, Olivier DelattreFrancois Doz, David W. Ellison, Richard J. Gilbertson, Scott L. Pomeroy, Michael D. Taylor, Peter Lichter, Stefan M. Pfister

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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.

Original languageEnglish (US)
Pages (from-to)473-484
Number of pages12
JournalActa Neuropathologica
Volume123
Issue number4
DOIs
StatePublished - Apr 1 2012

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Keywords

  • Medulloblastoma
  • Meta-analysis
  • Pediatric brain tumor
  • Subgroups

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Kool, M., Korshunov, A., Remke, M., Jones, D. T. W., Schlanstein, M., Northcott, P. A., Cho, Y. J., Koster, J., Schouten-Van Meeteren, A., Van Vuurden, D., Clifford, S. C., Pietsch, T., Von Bueren, A. O., Rutkowski, S., McCabe, M., Collins, V. P., Bäcklund, M. L., Haberler, C., Bourdeaut, F., ... Pfister, S. M. (2012). Molecular subgroups of medulloblastoma: An international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathologica, 123(4), 473-484. https://doi.org/10.1007/s00401-012-0958-8