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The methylation class (MC) RGNT (MC-RGNT) delineates RGNT from other neurocytic CNS tumors with similar histological features. We performed a comprehensive molecular analysis including whole-exome sequencing, RNAseq, and methylome on 9 tumors with similar histology, focusing on the immune microenvironment and cell of origin of RGNT. Three RGNT in this cohort were plotted within the MC-RGNT and characterized by FGFR1 mutation plus PIK3CA or NF1 mutations. RNAseq analysis, validated by immunohistochemistry, identified 2 transcriptomic groups with distinct immune microenvironments. The \u201ccold\u201d group was distinguishable by a low immune infiltration and included the 3 MC-RGNT and 1 MC-pilocytic astrocytoma; the \u201chot\u201d group included other tumors with a rich immune infiltration. Gene set enrichment analysis showed that the \u201ccold\u201d group had upregulated NOTCH pathway and mainly oligodendrocyte precursor cell and neuronal phenotypes, while the \u201chot\u201d group exhibited predominantly astrocytic and neural stem cell phenotypes. In silico deconvolution identified the cerebellar granule cell lineage as a putative cell of origin of RGNT. Our study identified distinct tumor biology and immune microenvironments as key features relevant to the pathogenesis and management of RGNT.<\/jats:p>","DOI":"10.1093\/jnen\/nlac074","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T13:39:54Z","timestamp":1660916394000},"page":"873-884","source":"Crossref","is-referenced-by-count":3,"title":["Immune Microenvironment and Lineage Tracing Help to Decipher Rosette-Forming Glioneuronal Tumors: A Multi-Omics Analysis"],"prefix":"10.1093","volume":"81","author":[{"given":"Julie","family":"Lerond","sequence":"first","affiliation":[{"name":"Institut du Cerveau\u2014Paris Brain Institute\u2014ICM, Inserm, CNRS, Sorbonne Universit\u00e9, AP-HP, SIRIC Curamus , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mony Chenda","family":"Morisse","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re\u2014Charles Foix, Service de Neurologie 2-Mazarin , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Letourneur","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, AP-HP, SIRIC Curamus , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coralie","family":"Gimonnet","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, AP-HP, SIRIC Curamus , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad","family":"Navarro","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re\u2014Charles Foix, Service de Neurochirurgie , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, UMS Production et Analyse des donn\u00e9es en Sciences de la vie et en Sant\u00e9, PASS, Plateforme Post-g\u00e9nomique de la Piti\u00e9-Salp\u00eatri\u00e8re , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Idbaih","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, AP-HP, Institut du Cerveau\u2014Paris Brain Institute\u2014ICM, Inserm, CNRS, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re\u2014Charles Foix, Service de Neurologie 2-Mazarin , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6564-6388","authenticated-orcid":false,"given":"Franck","family":"Bielle","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, AP-HP, Institut du Cerveau\u2014Paris Brain Institute\u2014ICM, Inserm, CNRS, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re\u2014Charles Foix, Service de Neuropathologie , Paris, France"},{"name":"AP-HP, H\u00f4pitaux Universitaires La Piti\u00e9 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