title: Characteristic chromosomal aberrations in sporadic cerebellar hemangioblastomas revealed by comparative genomic hybridization.
abstract: Hemangioblastomas (HBs) of the central nervous system are benign tumors and occur as sporadic (sp) tumors (75%) or as a manifestation of the von Hippel-Lindau (VHL) disease (25%). VHL-disease is an autosomal dominant disorder characterized by HBs of the central nervous system and retina, renal cell carcinoma (RCC), phaeochromocytoma (PHEO), islet tumors of the pancreas, and endolympatic sac tumors as well as cysts and cystadenoma in the kidney, pancreas and epididymis. In VHL patients a large spectrum of germline mutations in the VHL gene has been detected. In spHBs VHL alleles are reported to be inactivated in up to 50% of the tumors. To our knowledge the involvement of other genes in spHBs has not been investigated. To elucidate the oncogenesis of spHBs, we performed CGH on 10 spHBs to screen for chromosomal imbalances throughout the entire tumor genome. Aberrations most frequently detected are losses of chromosomes 3 (70%), 6 (50%), 9 (30%), and 18q (30%) and a gain of chromosome 19 (30%). Based on these frequencies and the co-occurrence of these aberrations in the analyzed tumors we hypothesize that loss of chromosome 3 (harboring the VHL gene) is an early event in the oncogenesis of spHBs, followed by loss of 6, and then losses of chromosomes 9, 18q and gain of chromosome 19. Comparison of the chromosomal imbalances in spHBs to those previously reported in RCCs and PHEOs reveals that the pathway of spHBs shows similarities to both the RCCs and PHEOs.
authors.affiliation: Department of Neurology, University Medical Center Nijmegen, The Netherlands.
authors.forename: S H
authors.initials: SH
authors.lastname: Sprenger
authors.forename: J M
authors.initials: JM
authors.lastname: Gijtenbeek
authors.forename: P
authors.initials: P
authors.lastname: Wesseling
authors.forename: R
authors.initials: R
authors.lastname: Sciot
authors.forename: F
authors.initials: F
authors.lastname: van Calenbergh
authors.forename: M
authors.initials: M
authors.lastname: Lammens
authors.forename: J W
authors.initials: JW
authors.lastname: Jeuken
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D002887:Chromosomes, Human, Pair 18 / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000235:genetics; D018325:Hemangioblastoma / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008025:Ligases / Q000172:deficiency / Q000235:genetics; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009006:Monosomy; D009693:Nucleic Acid Hybridization; D010673:Pheochromocytoma / Q000235:genetics; D014314:Trisomy; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human