title: Supratentorial primitive neuroectodermal tumors of the central nervous system frequently harbor deletions of the CDKN2A locus and other genomic aberrations distinct from medulloblastomas.
abstract: Supratentorial primitive neuroectodermal tumors (stPNETs) and medulloblastomas have long been thought to arise from a common cell type in the subventricular germinal matrix. Because of the infrequent occurrence of stPNETs, little is known about their genetic background. Here, we performed a genome-wide screening for DNA copy-number aberrations in 10 supratentorial PNETs using array-based comparative genomic hybridization (array-CGH). Comparing our findings with data from a previous array-CGH study on 47 medulloblastomas, we identified differences in the frequency of copy-number losses at chromosome regions 1p12-22.1 and 9p, and gains at 19p, all of them more frequently occurring in stPNETs. In contrast to previous reports, we detected chromosome 17 aberrations by array-CGH in 2/10 stPNETs. To validate our findings obtained by array-CGH, we analyzed the loci of interest by fluorescence in situ hybridization in an independent set of 11 stPNETs and found deletions of 9p21 in 5/11 tumors of the second set, three of them being homozygous. All 9p21 deletions were associated with loss of CDKN2A protein expression. Altogether, CDKN2A deletions were detected in 7/21 stPNETs including four homozygous deletions, whereas such deletions were only found in 4/112 medulloblastomas, all of these being heterozygous (P < 0.001). Gains of 19p (14% vs. 0% in medulloblastomas, P = 0.02) were found to be significantly more frequent in stPNETs, whereas gains of 17q (14% vs. 45% in medulloblastomas, P = 0.02) were confirmed to be more frequent in medulloblastomas. These data further support the hypothesis of two different tumor entities of embryonal neuroepithelial tumors with characteristic genetic aberrations. (c) 2007 Wiley-Liss, Inc.
authors.affiliation: Division Molecular Genetics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. s.pfister@dkfz.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfister
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: Grischa
authors.initials: G
authors.lastname: Toedt
authors.forename: Wiebke
authors.initials: W
authors.lastname: Werft
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Frank
authors.initials: F
authors.lastname: Mendrzyk
authors.forename: Andrea
authors.initials: A
authors.lastname: Wittmann
authors.forename: Frauke
authors.initials: F
authors.lastname: Devens
authors.forename: Katja
authors.initials: K
authors.lastname: von Hoff
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulozik
authors.forename: Bernhard
authors.initials: B
authors.lastname: Radlwimmer
authors.forename: Wolfram
authors.initials: W
authors.lastname: Scheurlen
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
mesh_terms: D002528:Cerebellar Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008527:Medulloblastoma / Q000235:genetics*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics*; D015173:Supratentorial Neoplasms / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16