A contemporary molecular view of diffuse gliomas with implications for diagnosis

Abstract

Diffuse gliomas are a family of neoplastic diseases characterized by widespread infiltration of central nervous system structures by tumor cells displaying glial differentiation. Traditionally characterized by morphologic features of lineage and histologic differentiation, we now understand that diffuse gliomas contain multiple discrete molecular subsets, each with their own clinical and genetic characteristics. In the current molecular era, the World Health Organization 4th Edition update introduced classes of diffuse glioma according to the status of isocitrate dehydrogenase mutation, 1p/19q co-deletion, histone H3 mutation, and BRAF mutation. Additional studies have demonstrated the subset-specific prognostic significance and grading implications of epidermal growth factor receptor amplification, CDKN2A/B homozygous deletion, TERT promoter mutations, and whole chromosome 7 gain and whole chromosome 10 loss (+7/−10). These findings represent the beginning of the molecular era of diagnosis and grading. Additional studies will likely refine our current conceptions and further advance our ability to stratify risk and direct therapies. In this review, we discuss the current understanding of the molecular classification of diffuse gliomas.