Journal Article

Papillary glioneuronal tumors: histological and molecular characteristics and diagnostic value of SLC44A1-PRKCA fusion

Lacroix, Ludovic, Pages, Melanie, Tauziede-Espariat, Arnault, Ridola, Vita, Gilles, Sophie, Andreiuolo, Felipe, Liu, Xiao-qiong, Castel, David, Fina, Frederic, Daudigeos-Dubus, Estelle, Lechapt-Zalcman, Emmanuele, Bridge, Julia A., Chretien, Fabrice, Puget, Stephanie, Polivka, Marc, Varlet, Pascale, Boddaert, Nathalie, Grill, Jacques

2015

Overview

Introduction 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.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BioMed Central part of Springer Science
• Subject: Adolescent / Adult / Antigens, CD - genetics / Antigens, CD34 - metabolism / Biomedical and Life Sciences / Biomedicine / Brain Neoplasms - diagnosis / Brain Neoplasms - genetics / Brain tumors / Child / Child, Preschool / Development and progression / Female / Gene mutations / Genetic aspects / Genotype / Glioma - diagnosis / Glioma - genetics / Health aspects / Humans / Identification and classification / Innovations / Life Sciences / Magnetic Resonance Imaging / Male / MAP Kinase Signaling System - genetics / Molecular diagnostic techniques / Mutation - genetics / Neoplasms, Neuroepithelial - diagnosis / Neoplasms, Neuroepithelial - genetics / Nerve Tissue Proteins - metabolism / Neurology / Neurosciences / Oncogene Fusion / Organic Cation Transport Proteins - genetics / Pathology / Protein Kinase C-alpha - genetics / Receptor, Fibroblast Growth Factor, Type 1 - genetics / Receptor, Fibroblast Growth Factor, Type 1 - metabolism / Young Adult