Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny.
Marion Classe, Hui Yao, Roger Mouawad, Chad J Creighton, Alice Burgess, Frederick Allanic, Michel Wassef, Xavier Leroy, Benjamin Verillaud, Geoffrey Mortuaire, Franck Bielle, Christophe Le Tourneau, Jean-Emmanuel Kurtz, David Khayat, Xiaoping Su, Gabriel G Malouf
Author Information
Marion Classe: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Sorbonnes-Universités, University Pierre and Marie Curie, Paris, France. Electronic address: marionclasse@hotmail.fr.
Hui Yao: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Roger Mouawad: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Sorbonnes-Universités, University Pierre and Marie Curie, Paris, France.
Chad J Creighton: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Division of Biostatistics, Department of Medicine and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Alice Burgess: Department of Otolaryngology-Head and Neck Surgery, Lariboisière Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Diderot Paris VII, Paris, France.
Frederick Allanic: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Sorbonnes-Universités, University Pierre and Marie Curie, Paris, France.
Michel Wassef: Department of Pathology, Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris-Diderot Paris VII, Paris, France.
Xavier Leroy: Department of Pathology, CHRU de Lille, Université Lille 2, Lille, France.
Benjamin Verillaud: Department of Otolaryngology-Head and Neck Surgery, Lariboisière Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Diderot Paris VII, Paris, France.
Geoffrey Mortuaire: Department of Otolaryngology-Head and Neck Surgery, CHRU de Lille, Université Lille 2, Lille, France.
Franck Bielle: Department of Neuropathology Raymond Escourolle, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, 75013, France.
Christophe Le Tourneau: Department of Drug Development and Innovation, Institut Curie, Saint-Cloud, France; INSERM U900 Research Unit, Saint-Cloud, France; Versailles-Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France.
Jean-Emmanuel Kurtz: Department of Hematology and Medical Oncology, CHRU Strasbourg, Hôpital Hautepierre, Strasbourg, France.
David Khayat: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Sorbonnes-Universités, University Pierre and Marie Curie, Paris, France.
Xiaoping Su: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gabriel G Malouf: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Sorbonnes-Universités, University Pierre and Marie Curie, Paris, France; Department of Hematology and Medical Oncology, CHRU Strasbourg, Hôpital Hautepierre, Strasbourg, France; Institut Génomique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch-Graffenstaden, France. Electronic address: gabriel.malouf@igbmc.fr.
Esthesioneuroblastoma (ENB) is a rare cancer of the olfactory mucosa, with no established molecular stratification to date. We report similarities of ENB with tumors arising in the neural crest and perform integrative analysis of these tumors. We propose a molecular-based subtype classification of ENB as basal or neural, both of which have distinct pathological, transcriptomic, proteomic, and immune features. Among the basal subtype, we uncovered an IDH2 R172 mutant-enriched subgroup (∼35%) harboring a CpG island methylator phenotype reminiscent of IDH2 mutant gliomas. Compared with the basal ENB methylome, the neural ENB methylome shows genome-wide reprogramming with loss of DNA methylation at the enhancers of axonal guidance genes. Our study reveals insights into the molecular pathogenesis of ENB and provides classification information of potential therapeutic relevance.
