Acta Neuropathol. 2012 April; 123(4): 465–472.
Molecular subgroups of medulloblastoma: the current consensus
1Division of Neurosurgery, Hospital for Sick Children, University of Toronto, Toronto, Canada
2Program in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, Toronto, Canada
3Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany
4Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
5Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany
6Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, USA
7Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
8Departments of Pathology, Ophthalmology and Oncology, Johns Hopkins University School of Medicine, Baltimore, USA
9Department of Pediatrics, Texas Children’s Cancer Center, Baylor College of Medicine, Houston, USA
10Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
11Department of Oncology, St. Jude Children’s Research Hospital, Memphis, USA
12Department of Pathology, St. Jude Children’s Research Hospital, Memphis, USA
13Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, USA
14Department of Neurology, Children’s Hospital Boston, Harvard Medical School, Boston, USA
Received October 6, 2011; Revised November 19, 2011; Accepted November 22, 2011.
Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause of morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication and stratification include clinical factors (age, presence of metastases, and extent of resection) as well as histological subgrouping (classic, desmoplastic, and large cell/anaplastic histology). Transcriptional profiling studies of medulloblastoma cohorts from several research groups around the globe have suggested the existence of multiple distinct molecular subgroups that differ in their demographics, transcriptomes, somatic genetic events, and clinical outcomes. Variations in the number, composition, and nature of the subgroups between studies brought about a consensus conference in Boston in the fall of 2010. Discussants at the conference came to a consensus that the evidence supported the existence of four main subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). Participants outlined the demographic, transcriptional, genetic, and clinical differences between the four subgroups. While it is anticipated that the molecular classification of medulloblastoma will continue to evolve and diversify in the future as larger cohorts are studied at greater depth, herein we outline the current consensus nomenclature, and the differences between the medulloblastoma subgroups.
Keywords: Medulloblastoma, Consensus, Subgroups, SHH, WNT, Group 3, Group 4
Michael D. Taylor, Email: mdtaylor/at/sickkids.ca.
Stefan M. Pfister, Email: s.pfister/at/dkfz.de.