title: Epidermal growth factor receptor gene amplification and expression in disseminated pediatric low-grade gliomas.
abstract: OBJECTIVE
  Pediatric low-grade gliomas (LGGs) are the largest group of central nervous system neoplasms in children. Although these tumors are generally benign, 5 to 10% of patients with pediatric LGGs present with leptomeningeal dissemination. The genetic and biological nature of these tumors is poorly understood. The authors looked for certain molecular abnormalities that may differentiate disseminated gliomas from the other pediatric LGGs.
  
  
  METHODS
  Comparative genomic hybridization (CGH) was applied to 18 pediatric LGGs. Six cases featuring disseminated pediatric LGGs were compared with 12 control cases involving nondisseminated pediatric LGGs. Fluorescence in situ hybridization (FISH) analysis and immunohistochemical analysis were used to highlight further specific genetic targets. The CGH revealed multiple chromosomal abnormalities in five of six cases with disseminated gliomas and in six of 12 control cases. No correlation was found between the number of chromosomal abnormalities and dissemination status. Amplification of chromosome 7 was noted in four of six cases with disseminated gliomas as opposed to one of 12 control cases (p = 0.02). The FISH analysis revealed epidermal growth factor receptor (EGFR) amplification in one case negative to chromosome 7 amplification by CGH, raising the amplification cases to five of six (p = 0.0038). Immunohistochemical analysis for EGFR was positive in six of six cases and in two of 12 control cases (p = 0.0015). At the end of a mean follow-up period of 7.2 years, all patients with disseminated gliomas are alive with variable but slow disease progression.
  
  
  CONCLUSIONS
  The high rate of EGFR gene amplification and protein expression in disseminated pediatric LGGs is intriguing and may have implications for our understanding of the role of EGFR in glioma genesis. Targeted therapies may be available for these children. Larger-scale studies are needed to establish further these findings.
authors.affiliation: Department of Pediatric Hemato-Oncology, Institute of Human-Genetics, and Institute of Hematology, Sheba Medical Center, Tel-Hashomer, Israel. uri.tabori@sickkids.ca
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
authors.forename: Shlomit
authors.initials: S
authors.lastname: Rienstein
authors.forename: Yaara
authors.initials: Y
authors.lastname: Dromi
authors.forename: Leonor
authors.initials: L
authors.lastname: Leider-Trejo
authors.forename: Shlomo
authors.initials: S
authors.lastname: Constantini
authors.forename: Yoav
authors.initials: Y
authors.lastname: Burstein
authors.forename: Rina
authors.initials: R
authors.lastname: Dvir
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.forename: Ayala
authors.initials: A
authors.lastname: Aviram
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D005910:Glioma / Q000235:genetics*; D006801:Humans; D006824:Hybridization, Genetic; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male
chemical_list: D066246:ErbB Receptors