Oligodendrogliomas:  new insights from the genetics and perspectives.
OBJECTIVE
Since the discovery, in 1994, of recurrent codeletion of chromosome regions 1p36/19q13 in oligodendrogliomas, genetics has accomplished significant advances improving our knowledge in biology of this tumor type and our clinical management of oligodendroglioma patients. Indeed, 1p36/19q13 has been shown successively to predict increased chemosensitivity and better prognosis, to be associated with frontal location in brain and classic oligodendroglioma morphology, to be mutually exclusive with high-level gene amplification, to be actually whole chromosome arms 1p/19q codeletion, to mediate a t(1;19)(q10;p10) and to be associated with IDH mutations. More recently, pivotal studies, using high-throughput approaches, have provided significant novel insights in the molecular oncogenesis of oligodendrogliomas.


RESULTS
Capicua homolog (Drosophila) (CIC) and Far Upstream element Binding Protein 1 (FUBP1) have been shown to be frequently mutated in 70 and 40% of 1p/19q codeleted oligodendrogliomas, respectively. The biological and clinical significance of these mutations remains unsettled. Additional recent studies have also demonstrated that 1p/19q codeleted oligodendrogliomas exhibit a proneural transcriptomic profile including overexpression of internexin alpha, a neuronal intermediate filament. Finally, 1p/19q codeleted and IDH-mutated tumors have been shown to be hypermethylated, suggesting a strong link between these both molecular alterations detected in the subgroup of oligodendrogliomas with better prognosis.


CONCLUSIONS
Next-generation molecular biology technologies have recently identified recurrent CIC and FUBP1 point mutations in 1p/19q codeleted and IDH-mutated oligodendrogliomas. Their clinical and biological values are under investigation.
Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMRS 975, Paris, France.
Agustí
A
Alentorn
Marc
M
Sanson
Ahmed
A
Idbaih
D000818:Animals; D001932:Brain Neoplasms / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009837:Oligodendroglioma / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D016601:RNA-Binding Proteins; D017384:Sequence Deletion
D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D016601:RNA-Binding Proteins; D007521:Isocitrate Dehydrogenase; D004265:DNA Helicases