title: Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease.
abstract: OBJECTIVE
  To define copy number alterations and gene expression signatures underlying pediatric high-grade glioma (HGG).
  
  
  METHODS
  We conducted a high-resolution analysis of genomic imbalances in 78 de novo pediatric HGGs, including seven diffuse intrinsic pontine gliomas, and 10 HGGs arising in children who received cranial irradiation for a previous cancer using single nucleotide polymorphism microarray analysis. Gene expression was analyzed with gene expression microarrays for 53 tumors. Results were compared with publicly available data from adult tumors.
  
  
  RESULTS
  Significant differences in copy number alterations distinguish childhood and adult glioblastoma. PDGFRA was the predominant target of focal amplification in childhood HGG, including diffuse intrinsic pontine gliomas, and gene expression analyses supported an important role for deregulated PDGFRalpha signaling in pediatric HGG. No IDH1 hotspot mutations were found in pediatric tumors, highlighting molecular differences with adult secondary glioblastoma. Pediatric and adult glioblastomas were clearly distinguished by frequent gain of chromosome 1q (30% v 9%, respectively) and lower frequency of chromosome 7 gain (13% v 74%, respectively) and 10q loss (35% v 80%, respectively). PDGFRA amplification and 1q gain occurred at significantly higher frequency in irradiation-induced tumors, suggesting that these are initiating events in childhood gliomagenesis. A subset of pediatric HGGs showed minimal copy number changes.
  
  
  CONCLUSIONS
  Integrated molecular profiling showed substantial differences in the molecular features underlying pediatric and adult HGG, indicating that findings in adult tumors cannot be simply extrapolated to younger patients. PDGFRalpha may be a useful target for pediatric HGG, including diffuse pontine gliomas.
authors.affiliation: St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Paugh
authors.forename: Chunxu
authors.initials: C
authors.lastname: Qu
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Liu
authors.forename: Martyna
authors.initials: M
authors.lastname: Adamowicz-Brice
authors.forename: Junyuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Dorine A
authors.initials: DA
authors.lastname: Bax
authors.forename: Beth
authors.initials: B
authors.lastname: Coyle
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barrow
authors.forename: Darren
authors.initials: D
authors.lastname: Hargrave
authors.forename: James
authors.initials: J
authors.lastname: Lowe
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.forename: Richard G
authors.initials: RG
authors.lastname: Grundy
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Baker
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D016371:Cranial Irradiation; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D020796:Receptor, Platelet-Derived Growth Factor alpha