Current Opinion on Molecular Characterization for GBM Classification in Guiding Clinical Diagnosis, Prognosis, and Therapy

Abstract

Glioblastoma (GBM) is highly invasive and the deadliest brain tumor in adults. It is characterized by inter-tumor and intra-tumor heterogeneity, short patient survival, and lack of effective treatment. Prognosis and therapy selection is driven by molecular data from gene transcription, genetic alterations and DNA methylation. The four GBM molecular subtypes are proneural, neural, classical, and mesenchymal. More effective personalized therapy heavily depends on higher resolution molecular subtype signatures, combined with gene therapy, immunotherapy and organoid technology. In this review, we summarize the principal GBM molecular classifications that guide diagnosis, prognosis, and therapeutic recommendations.

Keywords: DNA methylation-based subtype; genetic alteration-based subtype; glioblastoma; molecular heterogeneity; subtype-specific therapy; transcription-based subtype.

FIGURE 1

The process of molecular-based GBM classification: (A) GBM classification timeline and classical subtypes. (B) The relative overlap between subtypes from different classification methods.