title: Single-copy gain of chromosome 1q is a negative prognostic marker in pediatric nonependymal, nonpilocytic gliomas.
abstract: BACKGROUND
  Reports of genetic analyses on pediatric gliomas are few, and those tumors have been far less characterized than adult gliomas.
  
  
  OBJECTIVE
  To characterize the genetic and biological features of pediatric gliomas.
  
  
  METHODS
  We investigated 23 pediatric nonependymal, nonpilocytic gliomas for chromosomal copy number aberrations (CNAs) by comparative genomic hybridization (CGH), mutations of isocitrate dehydrogenase (IDH) genes by direct sequencing, and proliferative activity and expression of O-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry.
  
  
  RESULTS
  The most frequent CNA was single-copy gain of chromosome 1q, with 10 of 20 successfully investigated tumors showing the abnormality (50%). Other CNAs detected by CGH included gain on 7q (+7q) in 6, +9q in 5, +17q in 5, and + 7p in 4 cases. Gain of entire chromosome 7 was rare (2 cases), and codeletion of 1p and 19q was not detected. Gain of 1q was significantly predictive for shorter progression-free survival (PFS) and overall survival (OS), and even more closely associated with poor clinical outcome than histological grade (P = .0009 for PFS, P = .003 for OS by 1q status; P = .004 for PFS, P = .035 for OS by high-grade vs low-grade). Gain of 1q was also significantly correlated with proliferative activity (P = .0002), and tumors with 1q gain showed a trend toward higher MGMT expression (P = .27). Mutation of IDH1 gene was detected in only 2 of 17 tumors successfully analyzed.
  
  
  CONCLUSIONS
  Single copy gain of 1q is associated with biological features of pediatric gliomas, and is a negative prognostic marker in patients with those tumors.
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomoru
authors.initials: T
authors.lastname: Miwa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirose
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sasaki
authors.forename: Taketo
authors.initials: T
authors.lastname: Ezaki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawase
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D015254:DNA Modification Methylases / Q000096:biosynthesis / Q000235:genetics; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes