title: Papillary Tumor of the Pineal Region: A Distinct Molecular Entity.
abstract: Papillary tumor of the pineal region (PTPR) is a neuroepithelial brain tumor, which might pose diagnostic difficulties and recurs often. Little is known about underlying molecular alterations. We therefore investigated chromosomal copy number alterations, DNA methylation patterns and mRNA expression profiles in a series of 24 PTPRs. Losses of chromosome 10 were identified in all 13 PTPRs examined. Losses of chromosomes 3 and 22q (54%) as well as gains of chromosomes 8p (62%) and 12 (46%) were also common. DNA methylation profiling using Illumina 450k arrays reliably distinguished PTPR from ependymomas and pineal parenchymal tumors of intermediate differentiation. PTPR could be divided into two subgroups based on methylation pattern, PTPR group 2 showing higher global methylation and a tendency toward shorter progression-free survival (P = 0.06). Genes overexpressed in PTPR as compared with ependymal tumors included SPDEF, known to be expressed in the rodent subcommissural organ. Notable SPDEF protein expression was encountered in 15/19 PTPRs as compared with only 2/36 ependymal tumors, 2/19 choroid plexus tumors and 0/23 samples of other central nervous system (CNS) tumor entities. In conclusion, PTPRs show typical chromosomal alterations as well as distinct DNA methylation and expression profiles, which might serve as useful diagnostic tools.
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Heim
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Sill
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.affiliation: Centre de Pathologie et Neuropathologie Est, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron Cedex, France.|CRNL, INSERM U1028, CNRS UMR 5292, Equipe Neuro-oncologie et Neuro-inflammation, Université de Lyon, Lyon Cedex, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vasiljevic
authors.affiliation: Centre de Pathologie et Neuropathologie Est, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron Cedex, France.|CRNL, INSERM U1028, CNRS UMR 5292, Equipe Neuro-oncologie et Neuro-inflammation, Université de Lyon, Lyon Cedex, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Jouvet
authors.affiliation: CRNL, INSERM U1028, CNRS UMR 5292, Equipe Neuro-oncologie et Neuro-inflammation, Université de Lyon, Lyon Cedex, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Fèvre-Montange
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.affiliation: Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beschorner
authors.affiliation: Institute of Neurology (Edinger Institute), Goethe University, Frankfurt, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: Department of Pathology, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Kohlhof
authors.affiliation: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Hovestadt
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Johann
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Kristian W
authors.initials: KW
authors.lastname: Pajtler
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ruland
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Sperveslage
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Witt
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D004806:Ependymoma / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010870:Pineal Gland / Q000378:metabolism* / Q000473:pathology; D010871:Pinealoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger
keywords: DNA methylation; SPDEF; copy number alterations; ependymoma; mRNA expression; papillary tumor of the pineal region; prognosis