Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny

Marion Classe (1, 2) , Hui Yao (3) , Roger Mouawad (1, 2) , Chad Creighton (3) , Alice Burgess (4, 5) , Frederick Allanic (1, 2) , Michel Wassef (4, 5) , Xavier Leroy (6, 7) , Benjamin Verillaud (4, 5) , Geoffrey Mortuaire (6, 8) , Franck Bielle (1) , Christophe Le Tourneau (9, 10) , Jean-Emmanuel Kurtz (11, 12) , David Khayat (1, 2) , Xiaoping Su (3) , Gabriel Malouf (1, 2, 12, 11, 13)

1 CHU Pitié-Salpêtrière [AP-HP]
2 UPMC - Université Pierre et Marie Curie - Paris 6
3 MD Anderson Cancer Center [Houston]
4 Hôpital Lariboisière-Fernand-Widal [APHP]
5 UPD7 - Université Paris Diderot - Paris 7
6 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
7 JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837
8 LIRIC - Lille Inflammation Research International Center - U 995
9 Institut Curie [Paris]
10 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
11 Hôpital de Hautepierre [Strasbourg]
12 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
13 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

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 ( approximately 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.

Mots clés: DNA methylation; IDH2; basal; epigenetics; esthesioneuroblastomas; genetics; ki67; neural; sequencing; survival

Domaines: Cancer; Neurobiologie

Marion Classe, Hui Yao, Roger Mouawad, Chad Creighton, Alice Burgess, et al.. Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny. Cell Reports, 2018, 25 (3), pp.811-821. ⟨10.1016/j.celrep.2018.09.047⟩. ⟨hal-03671900⟩