Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters

J Neurooncol. 2017 Jan;131(2):403-412. doi: 10.1007/s11060-016-2313-8. Epub 2016 Nov 11.

Abstract

Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.

Keywords: Genetic subtypes; Gliomas; MRS; Predictive parameters.

MeSH terms

  • Adult
  • Aminolevulinic Acid / administration & dosage
  • Female
  • Glioma / diagnosis*
  • Glioma / diagnostic imaging
  • Glioma / genetics*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Mutation
  • Postoperative Care
  • Preoperative Care
  • Protoporphyrins / administration & dosage
  • Retrospective Studies
  • Sensitivity and Specificity
  • Supratentorial Neoplasms / diagnosis*
  • Supratentorial Neoplasms / diagnostic imaging
  • Supratentorial Neoplasms / genetics*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Protoporphyrins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Aminolevulinic Acid
  • protoporphyrin IX
  • Isocitrate Dehydrogenase