Molecular Genetics of Gliomas Drives New Classification and Therapy Paradigm
The 2016 revision of the WHO Classification of CNS Tumours incorporated molecular biomarkers alongside histology, fundamentally changing glioma diagnosis. Genome-wide profiling, DNA-methylation arrays, and NGS have identified clinically actionable markers such as IDH mutations, 1p/19q codeletion, and MGMT promoter methylation that refine subtype classification and predict outcomes. These advances are paving the way for precision medicine in neuro-oncology with novel pathogenesis-based therapeutic approaches.
The original study
Advances in the molecular genetics of gliomas - implications for classification and therapy.
- Authors
- Reifenberger G, Wirsching HG, Knobbe-Thomsen CB, Weller M
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Review
- PMID
- 28031556
Original abstract
Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.