title: Analysis of von hippel-lindau mutations with comparative genomic hybridization in sporadic and hereditary hemangioblastomas: possible genetic heterogeneity.
abstract: OBJECTIVE
  Hemangioblastomas (HBs) occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. In the majority of VHL-related HBs, inactivation of the VHL tumor suppressor gene (TSG), which is located on chromosome 3p25-26, is found. The VHL gene is assumed to be involved also in the development of sporadic HBs. In a previous study of chromosomal aberrations of sporadic HBs, multiple chromosomal imbalances were found in the majority of tumors. The aim of this study was to analyze further both sporadic HBs and VHL-related HBs to determine if these histopathologically identical tumors have a different genetic background.
  
  
  METHODS
  Sixteen sporadic HBs and seven VHL-related HBs were identified by clinical criteria and analyzed. Comparative genomic hybridization was used to screen for chromosomal imbalances throughout the entire HB genome. Additionally, mutation analysis of the VHL gene was performed using direct sequencing. Loss of chromosome 3 and multiple other chromosomal imbalances were found in the sporadic HBs, although only one imbalance, a loss of chromosome 3, was detected in the seven VHL-related HBs. Somatic VHL gene mutations were found in one third of sporadic HBs, whereas a mutation of the VHL gene was detected in all VHL-related HBs.
  
  
  CONCLUSIONS
  These results indicate that the molecular mechanisms underlying sporadic HBs and VHL-related HBs are different. Inactivation of the VHL gene is probably not the most important event in the tumorigenesis of sporadic HBs. Other mechanisms of inhibition of VHL protein function, or inactivation of other TSGs, on chromosome 3p or on other chromosomes, might be important in the development of sporadic HBs.
authors.affiliation: Department of Neurology, University Medical Center Nijmegen, The Netherlands. j.gijtenbeek@czzoneu.azn.nl
authors.forename: Johanna M M
authors.initials: JM
authors.lastname: Gijtenbeek
authors.forename: Bram
authors.initials: B
authors.lastname: Jacobs
authors.forename: Sandra H E
authors.initials: SH
authors.lastname: Sprenger
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Eleveld
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Frank
authors.initials: F
authors.lastname: van Calenbergh
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.forename: Judith W M
authors.initials: JW
authors.lastname: Jeuken
mesh_terms: D000328:Adult; D000368:Aged; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D018740:Genetic Heterogeneity; D018325:Hemangioblastoma / Q000235:genetics*; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009693:Nucleic Acid Hybridization; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human