Molecular changes in gliomas

Abstract

Despite optimal clinical treatment, the prognosis for gliomas remains poor, and little progress has been observed during the last few years. Meanwhile, understanding of glioma oncogenesis has improved greatly. This review focuses on recent advances in molecular biology of glial tumors, with particular emphasis on lineage markers, genetic mechanisms underlying tumor progression, new diagnostic and prognostic markers, and potential therapeutic targets. The question of the cell of origin, illustrated by the evidence of tumor-derived multipotent progenitors, by the animal models of gliomas, and by lineage markers such as Olig1/2 markers, remains unsolved. Genotype/phenotype correlation studies have identified early and late genetic alterations related either to astrocytic or oligodendroglial phenotype. They complement the existing World Health Organization morphologic classification and provide additional prognostic markers such as 1p/19q deletion in oligodendrogliomas. Most of these genetic alterations result in the disruption of three main cellular systems: RB1, P53, and tyrosine kinase receptor pathways. New gene alterations have also been identified in glioma, promoting mitotic signal transduction, cell cycle regulation, apoptosis, angiogenesis, or invasion. Gene and protein profiling has been correlated with outcome. Management of gliomas, especially oligodendrogliomas with 1p19q deletion, benefits from advances in molecular genetics. A better understanding of the molecular pathogenesis and cellular lineage of gliomas will improve tumor classification and define more reliable prognostic markers. There is a hope that it will also lead to novel targets for therapy.