Predictive biomarkers in adult gliomas: the present and the future

Curr Opin Oncol. 2013 Nov;25(6):689-94. doi: 10.1097/CCO.0000000000000002.

Abstract

Purpose of review: This review summarizes recent studies on the predictive value of molecular markers in adult gliomas, including 1p/19q codeletion, MGMT methylation, IDH mutation and markers identified using omics and next-generation sequencing studies.

Recent findings: The long-term results of the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer trials in anaplastic oligodendroglial glioma have shown that the 1p/19q codeletion predicts an overall survival benefit from early PCV (procarbazine CCNU vincristine) chemotherapy. This benefit can also be predicted using gene expression-based molecular subtypes of gliomas while the predictive value of the IDH mutation in this context requires further study. In elderly patients with glioblastoma, the analysis of MGMT methylation status in two phase III trials suggests that this alteration may guide treatment decisions; however, this finding still needs confirmation in prospective studies. Omics and next-generation sequencing studies have identified additional potential predictive markers. In particular, IDH mutations, BRAF V600E mutations and FGFR gene fusions might predict efficacy of therapies targeted against these alterations.

Summary: Currently, the 1p/19q codeletion is the only well established predictive marker with clinical utility. However, it is likely that other molecular markers such as MGMT methylation, IDH mutation and those identified using omics and next-generation sequencing studies will further guide treatment decisions in adult gliomas.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Chromosome Deletion
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / drug therapy
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Mutation
  • Precision Medicine / trends*
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • DNA Repair Enzymes