title: Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas.
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.
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.kool@dkfz.de
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.forename: Maria
authors.initials: M
authors.lastname: Schlanstein
authors.forename: Paul A
authors.initials: PA
authors.lastname: Northcott
authors.forename: Yoon-Jae
authors.initials: YJ
authors.lastname: Cho
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.forename: Antoinette
authors.initials: A
authors.lastname: Schouten-van Meeteren
authors.forename: Dannis
authors.initials: D
authors.lastname: van Vuurden
authors.forename: Steven C
authors.initials: SC
authors.lastname: Clifford
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Andre O
authors.initials: AO
authors.lastname: von Bueren
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Martin
authors.initials: M
authors.lastname: McCabe
authors.forename: V Peter
authors.initials: VP
authors.lastname: Collins
authors.forename: Magnus L
authors.initials: ML
authors.lastname: Bäcklund
authors.forename: Christine
authors.initials: C
authors.lastname: Haberler
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Francois
authors.initials: F
authors.lastname: Doz
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
authors.forename: Scott L
authors.initials: SL
authors.lastname: Pomeroy
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult; D017677:Age Distribution; D002528:Cerebellar Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D015331:Cohort Studies; D003582:Cytogenetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007391:International Cooperation; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008527:Medulloblastoma / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D046228:Microarray Analysis; D015999:Multivariate Analysis; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D059467:Transcriptome; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C073616:atrial natriuretic factor receptor C; D053823:Hedgehog Proteins; C496946:KCNA1 protein, human; D051662:Kv1.1 Potassium Channel; D017461:Receptors, Atrial Natriuretic Factor; C509239:SHH protein, human; D051153:Wnt Proteins