title: Papillary glioneuronal tumors: histological and molecular characteristics and diagnostic value of SLC44A1-PRKCA fusion.
abstract: BACKGROUND
  Papillary Glioneuronal Tumor (PGNT) is a grade I tumor which was classified as a separate entity in the World Health Organization Classification of the Central Nervous System 2007 in the group of mixed glioneuronal tumors. This tumor is rare and subclassifying PGNT represents a challenge. Recently, a fusion between SLC44A1 and PRKCA which encodes a protein kinase C involved in MAPK signaling pathway has been described in two studies (five cases). The current study aimed at raising the cytogenetic, histological and molecular profiles of PGNT and to determine if SLC44A1-PRKCA fusion represented a specific diagnostic marker to distinguish it from other glioneuronal tumors.
  
  
  RESULTS
  We report on four pediatric cases of PGNT, along with clinico-radiologic and immunohistological features for which SLC44A1-PRKCA fusion assessment by fluorescence in situ hybridization, BRAF V600E and FGFR1 mutation by immunohistochemistry and direct DNA sequencing and KIAA1549-BRAF fusion by RT-PCR were performed. MAPK signaling pathway activation was investigated using phospho-ERK immunohistochemistry and western blot. We analyzed fifteen cases of tumors with challenging histological or clinical differential diagnoses showing respectively a papillary architecture or periventricular location (PGNT mimics). fluorescence in situ hybridization analysis revealed a constant SLC44A1-PRKCA fusion signal in all PGNTs. None of PGNT mimics showed the SLC44A1-PRKCA fusion signal pattern. All PGNTs were negative for BRAF V600E and FGFR1 mutation, and KIAA1549-BRAF fusion. Phospho-ERK analysis provides arguments for the activation of the MAPK signaling pathway in these tumors.
  
  
  CONCLUSIONS
  Here we confirmed and extended the molecular data on PGNT. These results suggest that PGNT belong to low grade glioma with MAPK signaling pathway deregulation. SLC44A1-PRKCA fusion seems to be a specific characteristic of PGNT with a high diagnostic value and detectable by FISH.
authors.affiliation: Department of Neuropathology, Sainte-Anne Hospital, Paris, France. m.pages@ch-sainte-anne.fr.|Paris Descartes University, Sorbonne Paris Cité, Paris, France. m.pages@ch-sainte-anne.fr.|Institut National de la Sante et de la Recherche Medicale, INSERM CEAUnit1000, "Imaging & Psychiatry", University Paris Sud, 91400, Orsay, France. m.pages@ch-sainte-anne.fr.
authors.forename: Melanie
authors.initials: M
authors.lastname: Pages
authors.affiliation: Gustave Roussy, Département de Biologie et Pathologie Médicales, Villejuif, F-94805, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
authors.forename: Arnault
authors.initials: A
authors.lastname: Tauziede-Espariat
authors.affiliation: CNRS, UMR8203, Villejuif, F-94805, France.|Univ Paris-Sud, UMR8203, Villejuif, F-94805, France.|Gustave Roussy, UMR8203, Villejuif, F-94805, France.|Gustave Roussy, Département de Cancérologie de l'Enfant et de l'Adolescent, Villejuif, F-94805, France.
authors.forename: David
authors.initials: D
authors.lastname: Castel
authors.affiliation: CNRS, UMR8203, Villejuif, F-94805, France.|Univ Paris-Sud, UMR8203, Villejuif, F-94805, France.|Gustave Roussy, UMR8203, Villejuif, F-94805, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Daudigeos-Dubus
authors.affiliation: Gustave Roussy, Département de Cancérologie de l'Enfant et de l'Adolescent, Villejuif, F-94805, France.|Department of Pediatric Hematology and Oncology, Catholic University, Rome, Italy.
authors.forename: Vita
authors.initials: V
authors.lastname: Ridola
authors.affiliation: Service de transfert d'Oncologie Biologique, LBM APHM, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gilles
authors.affiliation: Service de transfert d'Oncologie Biologique, LBM APHM, Marseille, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Fina
authors.affiliation: Department of Neuropathology, Sainte-Anne Hospital, Paris, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Andreiuolo
authors.affiliation: Department of Pathology, Lariboisière Hospital, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Polivka
authors.affiliation: Department of Neuropathology, Sainte-Anne Hospital, Paris, France.|Laboratoire d'Anatomie Pathologique, CHU de Caen, France, UMR6301-ISTCT CNRS, CEA, Université de Caen Basse-Normandie, GIP, Cyceron, France.
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Lechapt-Zalcman
authors.affiliation: Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Puget
authors.affiliation: Department of Pediatric Neuroradiology, Necker Enfants Malades Hospital, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical center, Omaha, NE, USA.|Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Xiao-Qiong
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical center, Omaha, NE, USA.|Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.|Department of Orthopaedic Surgery, University of Nebraska Medical Center, Omaha, NE, USA.|Institut Pasteur, Human Histopathology and Animal Models Unit, Infection and Epidemiology Department, Paris, France.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bridge
authors.affiliation: CNRS, UMR8203, Villejuif, F-94805, France.|Univ Paris-Sud, UMR8203, Villejuif, F-94805, France.|Gustave Roussy, UMR8203, Villejuif, F-94805, France.|Gustave Roussy, Département de Cancérologie de l'Enfant et de l'Adolescent, Villejuif, F-94805, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.affiliation: Department of Neuropathology, Sainte-Anne Hospital, Paris, France.|Paris Descartes University, Sorbonne Paris Cité, Paris, France.|Institut Pasteur, Human Histopathology and Animal Models Unit, Infection and Epidemiology Department, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chretien
authors.affiliation: Department of Neuropathology, Sainte-Anne Hospital, Paris, France.|Paris Descartes University, Sorbonne Paris Cité, Paris, France.|Institut National de la Sante et de la Recherche Medicale, INSERM CEAUnit1000, "Imaging & Psychiatry", University Paris Sud, 91400, Orsay, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Varlet
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D018952:Antigens, CD34 / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics; D018302:Neoplasms, Neuroepithelial / Q000175:diagnosis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050596:Oncogene Fusion; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D051571:Protein Kinase C-alpha / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D009419:Nerve Tissue Proteins; D027701:Organic Cation Transport Proteins; C510732:SLC44A1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051571:Protein Kinase C-alpha