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, 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
Abstract
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.
Keywords: DNA methylation; IDH2; basal; epigenetics; esthesioneuroblastomas; genetics; ki67; neural; sequencing; survival.
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
Source: PubMed