Tumor cells with neuronal intermediate progenitor features define a subgroup of 1p/19q co‐deleted anaplastic gliomas. (28th October 2016)

• Record Type: Journal Article
• Authors: Bielle, Franck; Ducray, François; Mokhtari, Karima; Dehais, Caroline; Adle‐Biassette, Homa; Carpentier, Catherine; Chanut, Anaïs; Polivka, Marc; Poggioli, Sylvie; Rosenberg, Shai; Giry, Marine; Marie, Yannick; Duyckaerts, Charles; Sanson, Marc; Figarella‐Branger, Dominique; Idbaih, Ahmed
• Other Names: Desenclos Christine investigator.; Sevestre Henri investigator.; Menei Philippe investigator.; Rousseau Audrey investigator.; Godard Joel investigator.; Viennet Gabriel investigator.; Carpentier Antoine investigator.; Eimer Sandrine investigator.; Loiseau Hugues investigator.; Dam‐Hieu Phong investigator.; Quintin‐Roué Isabelle investigator.; Guillamo Jean‐Sebastien investigator.; Lechapt‐Zalcman; Emmanuelle investigator.; Kemeny Jean‐Louis investigator.; Khallil Toufik investigator.; Cazals‐Hatem Dominique investigator.; Faillot Thierry investigator.; Carpiuc Ioana investigator.; Richard Pomone investigator.; Le Guerinel Caroline investigator.; Gaultier Claude investigator.; Tortel Marie‐Christine investigator.; Aubriot‐Lorton Marie‐Hélène investigator.; Ghiringhelli François investigator.; Adam Clovis investigator.; Parker Fabrice investigator.; Maurage Claude‐Alain investigator.; Ramirez Carole investigator.; Marcel Gueye Edouard investigator.; Labrousse François investigator.; Jouvet Anne investigator.; Chinot Olivier investigator.; Bauchet Luc investigator.; Rigau Valérie investigator.; Beauchesne Patrick investigator.; Gauchotte Guillaume investigator.; Campone Mario investigator.; Loussouarn Delphine investigator.; Fontaine Denys investigator.; Vandenbos Fanny investigator.; Blechet Claire investigator.; Fesneau Mélanie investigator.; Yves Delattre Jean investigator.; Elouadhani‐Hamdi Selma investigator.; Ricard Damien investigator.; Larrieu‐Ciron Delphine investigator.; Levillain Pierre‐Marie investigator.; Colin Philippe investigator.; Diebold Marie‐Danièle investigator.; Chiforeanu Danchristian investigator.; Vauléon Elodie investigator.; Langlois Olivier investigator.; Laquerrière Annie investigator.; Motsuo Fotso Marie Janette investigator.; Peoc'h Michel investigator.; Andraud Marie investigator.; Runavot Gwenaelle investigator.; Chenard Marie‐Pierre investigator.; Noel Georges investigator.; Gaillard Stéphane investigator.; Villa Chiara investigator.; Desse Nicolas investigator.; Cohen‐Moyal Elisabeth investigator.; Uro‐Coste Emmanuelle investigator.; Dhermain Frédéric investigator.;
• Is Part Of: Brain pathology. Volume 27:Number 5(2017)
• Page Start: 567
• Page End: 579
• Publication Date: 2016-10-28
• Subjects: anaplastic oligodendroglioma -- 1p/19q co‐deletion -- embryonic subventricular zone -- neuronal intermediate progenitor; Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12434
• Languages: English
• ISSNs: 1015-6305

Abstract

Abstract: The integrated diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q co‐deleted, grade III (O3 id ) is a histomolecular entity that WHO 2016 classification distinguished from other diffuse gliomas by specific molecular alterations. In contrast, its cell portrait is less well known. The present study is focused on intertumor and intratumor, cell lineage‐oriented, heterogeneity in O3 id . Based on pathological, transcriptomic and immunophenotypic studies, a novel subgroup of newly diagnosed O3 id overexpressing neuronal intermediate progenitor (NIP) genes was identified. This NIP overexpression pattern in O3 id is associated with: (i) morphological and immunohistochemical similarities with embryonic subventricular zone, (ii) proliferating tumor cell subpopulation with NIP features including expression of INSM1 and no expression of SOX9, (iii) mutations in critical genes involved in NIP biology and, (iv) increased tumor necrosis. Interestingly, NIP tumor cell subpopulation increases in O3 id recurrence compared with paired newly diagnosed tumors. Our results, validated in an independent cohort, emphasize intertumor and intratumor heterogeneity in O3 id and identified a tumor cell subpopulation exhibiting NIP characteristics that is potentially critical in oncogenesis of O3 id . A better understanding of spatial and temporal intratumor cell heterogeneity in O3 id will open new therapeutic avenues overcoming resistance to current antitumor treatments.