Oligodendrogliomas are primary tumours of the central nervous system<\/strong> with morphological characteristics of oligodendrocytes. It has been proposed that the precursors of oligodendrocytes or OPC,<\/strong> for Oligodendrocyte Progenitor Cells<\/em>, are the cells that cause oligodendrogliomas.<\/strong> They are generated from neural stem cells during development. At birth, the latter differentiate into oligodendrocytes, the cells responsible for the myelination of neurons.<\/strong> OPC persist in the adult brain where they are the most proliferative cell type.<\/strong><\/p>\n <\/p>\n The genetics of oligodendrogliomas in humans is well known and shows frequent mutations in several genes. For example, the mutation of the enzyme Isocitrate Dehydrogenase 1 (IDH1R132H) is found in 100% of oligodendrogliomas.<\/strong> In physiological condition, IDH1 allows the conversion of isocitrate to a-cetoglutarate,<\/strong> but when mutated, it acquires a new function: that of reducing a-cetoglutarate to D-2-hydroxyglutarate, an oncometabolite that accumulates in cells<\/strong>. Similarly, all oligodendrogliomas have a co-deletion of chromosomes 1p and 19q<\/strong>. It is interesting to note that the 19q arm codes for the CIC (Capicua) protein which is found mutated in 50-70% of oligodendrogliomas.<\/strong> Physiologically, CIC decreases cell proliferation and promotes cell differentiation; thus its mutation in oligodendrogliomas results in a non-functional protein.<\/strong><\/p>\n <\/p>\n New therapies are needed for oligodendrogliomas<\/strong>, especially for the more aggressive forms that can progress to glioblastoma. \u00a0Although the mutations present in human tumours are well characterized, the research community does not have a study model for understanding the formation and development of oligodendrogliomas. Possessing in vivo models to study the initiation, formation and progression of oligodendrogliomas remains a major challenge in order to discover functional treatments.<\/strong><\/p>\n <\/p>\n Emmanuelle Huillard’s research team proposes to create and characterize a new in vivo model to induce HDI1 and CIC mutations in OPC<\/strong>. Our working hypothesis is that the synergy of these mutations will induce an increase in proliferation to the detriment of OPC differentiation, two behaviours that are modified during tumorigenesis.<\/strong><\/p>\n <\/p>\n By developing and describing this model, which summarizes the genetics of human oligodendrogliomas,<\/strong> we hope to provide the scientific community with a biological tool for understanding the formation of these tumors as well as for preclinical studies.<\/strong><\/p>\n <\/p>\n Sandra Joppe,<\/p>\n post-PhD, Emmanuelle Huillard’s research team<\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":" Functional consequences of HDI1 and CIC mutations on the cells of origin of oligodendrogliomas Oligodendrogliomas are primary tumours of the […]<\/p>\n","protected":false},"author":6,"featured_media":1765,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[28],"tags":[],"class_list":["post-1764","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-neuro-vulgarise-en-2"],"acf":[],"yoast_head":"\n