Klin Padiatr 2011; 223 - A9
DOI: 10.1055/s-0031-1292590

Molecular subtypes in medulloblastoma: an International meta-analysis for profiles, genetic aberrations, clinicopathological features AND SURVIVAL

M Kool 1, 2, J Koster 2, M Remke 1, A Korshunov 1, T Hielscher 1, H Witt 1, P Northcott 1, 3, A Schouten-van Meeteren 2, S Clifford 4, T Pietsch 5, A von Buehren 6, S Rutkowski 6, Y Cho 7, R Versteeg 2, C Haberler 8, D Ellison 9, R Gilbertson 9, S Pomeroy 7, F Doz 10, O Delattre 10, M Taylor 3, S Pfister 1
  • 1German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 2Academic Medical Center, Amsterdam, the Netherlands
  • 3Hospital for Sick Children, Toronto, Canada
  • 4Northern Institute for Cancer Research, Newcastle, UK
  • 5Institut for Neuropathology, Bonn, Germany
  • 6University Medical Center, Hamburg Eppendorf, Germany
  • 7Children's Hospital Boston and Harvard Medical School, Boston, USA
  • 8Institut for Neurology, Medical University, Vienna, Austria.
  • 9St Jude Children's Research Hospital, Memphis, USA
  • 10Institut Curie, Paris, France

Medulloblastoma is the most common malignant pediatric brain tumor. Already for a long time it is known that it is a very heterogeneous disease and indeed recent studies from several groups have shown that medulloblastoma comprises a collection of clinically and molecularly distinct subtypes. A better understanding of each of these molecular subtypes is now needed to improve treatment strategies and the overall survival of patients and ultimately also the quality of life for those that survive medulloblastoma. For that we have brought together all the recent molecular studies on medulloblastoma into one database (R2.amc.nl) to perform a meta-analysis on these molecular subtypes in a large series of tumors. Data from 6 independent series of medulloblastomas (n=521) were collected and analyzed. All cases were analyzed by expression profiling and most cases were also analyzed for genetic aberrations using SNP or CGH arrays. Other data collected for most cases included histology, gender, age at diagnosis, metastatic stage, and survival. Recent profiling studies have shown that medulloblastoma comprises 4–6 molecular subtypes. The consensus in the field is now that there are 4 major subtypes of medulloblastoma and each of these major subtypes may be further subdivided into smaller groups based on additional characteristics within these subtypes. Two of the most distinct subtypes are characterized by activated WNT or activated SHH signalling, while the other two subtypes are more related to each other. They show elevated expression of neuronal differentiation and/or photoreceptor genes. They are much more frequent in males than in females and they are strongly associated with metastatic disease. A subgroup of these non-WNT/non-SHH tumors, characterized by a high frequency of MYC amplifications, has an extreme poor outcome. We will present data of these meta-analyses and give an overview of the characteristics for each of these molecular subtypes.