Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny.
Fiche publication
Date publication
octobre 2018
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KURTZ Jean-Emmanuel, Pr MALOUF Gabriel
Tous les auteurs :
Classe M, Yao H, Mouawad R, Creighton CJ, Burgess A, Allanic F, Wassef M, Leroy X, Verillaud B, Mortuaire G, Bielle F, Le Tourneau C, Kurtz JE, Khayat D, Su X, Malouf GG
Lien Pubmed
Résumé
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.
Mots clés
DNA methylation, IDH2, basal, epigenetics, esthesioneuroblastomas, genetics, ki67, neural, sequencing, survival
Référence
Cell Rep. 2018 Oct 16;25(3):811-821.e5