Actionable Molecular Biomarkers in Primary Brain Tumors

Verena Staedtke, Omar Dildar A Dzaye, Matthias Holdhoff

Research output: Contribution to journalArticle

Abstract

Recent genome-wide studies of malignancies of the central nervous system (CNS) have revolutionized our understanding of the biology of these tumors. This newly gained knowledge provides a wealth of opportunity for biomarker-driven clinical research. To date, however, only few of the available molecular markers truly influence clinical decision-making and treatment. The most widely validated markers in neuro-oncology presently are: (i) . MGMT promoter methylation as a prognostic and predictive marker in glioblastoma; (ii) codeletion of 1p and 19q differentiating oligodendrogliomas from astrocytomas; (iii) . IDH1/2 mutations; and (iv) select pathway-associated mutations. This article focuses on currently impactful biomarkers in adult and pediatric brain cancers and it provides a perspective on the direction of research in this field. Genome-wide studies unveiled a plethora of cancer specific genetic alterations. The recently updated World Health Organization classification of brain tumors (2016) for the first time includes molecular markers to determine subclasses of gliomas and medulloblastomas. However, thus far only few markers are sufficiently characterized to impact the clinical practice in patients with CNS cancers. . MGMT promoter methylation in high-grade astrocytomas and codeletion of 1p/19q in oligodendrogliomas are proven . prognostic and predictive markers that play a role in standard practice, and mutations of IDH1 or IDH2 are of strong prognostic value in gliomas. The true clinical impact of other markers in gliomas has yet to be determined.Cancer-specific markers are of increasing importance in patient selection for clinical trials and marker- rather than diagnosis-driven studies. Some of these markers enable us to pair available targeted drugs with subpopulations of tumors based on a biological rationale and a true drug target (e.g., . BRAF inhibitors in . V600E mutated tumors, '. basket trials').Further prospective research is needed to formally validate individual markers. This needs to also include the methodological standardization of testing to allow for reliable interlaboratory concordance rates.

Original languageEnglish (US)
JournalTrends in Cancer
DOIs
StateAccepted/In press - 2016

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Keywords

  • Biomarker
  • BRAF mutation
  • Codeletion
  • Codeletion of 1p/19q
  • Glioblastoma
  • Glioma
  • IDH mutation
  • Medulloblastoma
  • MGMT promoter methylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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