Oligodendrogliomas: new insights from the genetics and perspectives

Curr Opin Oncol. 2012 Nov;24(6):687-93. doi: 10.1097/CCO.0b013e328357f4ea.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / classification
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • DNA Helicases / genetics
  • DNA-Binding Proteins / genetics
  • Genetic Association Studies
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Oligodendroglioma / classification
  • Oligodendroglioma / enzymology
  • Oligodendroglioma / genetics*
  • Point Mutation
  • RNA-Binding Proteins
  • Sequence Deletion

Substances

  • DNA-Binding Proteins
  • FUBP1 protein, human
  • RNA-Binding Proteins
  • Isocitrate Dehydrogenase
  • DNA Helicases