Beyond grade: molecular pathology of malignant gliomas

Abstract

High-grade gliomas (HGGs) represent a heterogenous group of tumors and account for most primary brain tumors. Despite aggressive therapies, they are invariably associated with poor patient outcome. These tumors include the anaplastic (World Health Organization [WHO] grade III) histologies of astrocytomas, oligodendrogliomas, and ependymomas and the WHO grade IV glioblastoma multiforme (GBM). The recent elucidation of the fundamental molecular alterations associated with these tumors has begun to unravel the critical events in their tumorigenesis but for the most part has done little to alter patient survival. Prognostication for patients with these tumors has relied principally on tumor grade and clinical factors (age, performance status, and so on) and has been inexact at best in identifying those with long-term survival potential. An even greater challenge has been to identify predictive biomarkers of therapy in the hope of tailoring a patient's therapy based on their tumor's molecular characteristics. This review discusses the molecular pathology of high-grade gliomas, with particular emphasis on anaplastic astrocytomas and GBMs because these represent the most common forms of malignant gliomas. It also focuses on the molecular signatures defined by large-scale gene expression profiling experiments because these studies are at the forefront in developing new biomarkers and identifying new therapeutic targets.