title: Adult and pediatric medulloblastomas are genetically distinct and require different algorithms for molecular risk stratification.
abstract: OBJECTIVE
  Medulloblastoma (MB) is the most common malignant brain tumor in children, whereas it rarely presents in adults. We aimed to identify genetic aberrations in 146 adult MBs to evaluate age-dependent differences in tumor biology and adapt age-specific risk stratification models.
  
  
  METHODS
  As a screening set, we studied a cohort of 34 adult MBs by using array-based comparative genomic hybridization comparing molecular results with clinical data. DNA copy number aberrations identified as possible prognostic markers were validated in an independent cohort of 112 adult patients with MB by fluorescent in situ hybridization analysis. Results were compared with the data obtained from 404 pediatric patients with MB.
  
  
  RESULTS
  CDK6 amplification, 10q loss, and 17q gain are the most powerful prognostic markers in adult MB. Whereas MYC/MYCN oncogene amplifications had a high prognostic value in pediatric MB, these aberrations were rarely observed in adult tumors. Surprisingly, adult MBs with 6q deletion and nuclear beta-catenin activation did not share the excellent prognosis with their pediatric counterparts.
  
  
  CONCLUSIONS
  Adult MB is distinct from pediatric MB in terms of genomic aberrations and their impact on clinical outcomes. Therefore, adult MBs require age-specific risk stratification models. We propose a molecular staging system involving three distinct risk groups based on DNA copy number status of 10q and 17q.
authors.affiliation: Clinical Cooperation Unit Neuropathology, Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: Wiebke
authors.initials: W
authors.lastname: Werft
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Marina
authors.initials: M
authors.lastname: Ryzhova
authors.forename: Hendrik
authors.initials: H
authors.lastname: Witt
authors.forename: Dominik
authors.initials: D
authors.lastname: Sturm
authors.forename: Andrea
authors.initials: A
authors.lastname: Wittmann
authors.forename: Anna
authors.initials: A
authors.lastname: Schöttler
authors.forename: Jörg
authors.initials: J
authors.lastname: Felsberg
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Wolfram
authors.initials: W
authors.lastname: Scheurlen
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kulozik
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
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; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics; D018287:Carcinoma, Large Cell / Q000145:classification / Q000235:genetics / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D018570:Risk Assessment; D046888:Tissue Array Analysis; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin