The WHO 2007 glioma classification system (based primarily on tumour histology) resulted in considerable interobserver variability and substantial variation in patient survival within grades. Furthermore, few risk factors for glioma were known. Discoveries over the past decade have deepened our understanding of the molecular alterations underlying glioma and have led to the identification of numerous genetic risk factors. The advances in molecular characterization of glioma have reframed our understanding of its biology and led to the development of a new classification system for glioma. The WHO 2016 classification system comprises five glioma subtypes, categorized by both tumour morphology and molecular genetic information, which led to reduced misclassification and improved consistency of outcomes within glioma subtypes. To date, 25 risk loci for glioma have been identified and several rare inherited mutations that might cause glioma in some families have been discovered. This Review focuses on the two dominant trends in glioma science: the characterization of diagnostic and prognostic tumour markers and the identification of genetic and other risk factors. An overview of the many challenges still facing glioma researchers is also included.
Glioma incidence differs by age, sex, ethnicity and geography whereas glioma survival varies by tumour subtype, age and sex.
In the past decade, multiple discoveries have expanded our understanding of glioma and led to a new classification system (WHO 2016) that integrates molecular alterations and histology.
The WHO 2016 classification system defines five glioma subtypes that have improved homogeneity in their clinical outcomes.
Twenty-five risk loci for glioma and several rare inherited mutations that might cause glioma in some families have been identified; however, ionizing radiation is the only confirmed environmental risk factor.
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The authors thank K. Probst for his artistic support and T. Rice, S. Lin, G. Warrier, P. Chunduru and Y. Zhang for their analytical support. The authors also thank L. McCoy, J. Phillips, J. Clarke, P. Bracci, Q. Ostrom, J. Barnholtz-Sloan, C. Kruchko, R. Jenkins, J. Eckel-Passow, A. Perry, M. Pekmezci, S. Chang and M. Berger for help with data, their ongoing insights and intellectual support. The authors’ research work is supported by NIH grant number P50CA09725 and the loglio collective (to all four authors), R01 CA207360 (to A.M.M., J.K.W. and M.R.W.), the Lewis Chair in Brain Tumor Research (held by M.R.W.) and the Robert Magnin Newman Chair in Neuro-oncology (held by J.K.W.).
Nature Reviews Neurology thanks M. Hegi, W. Wick and J. Schwartzbaum for their contribution to the peer review of this work.
The authors declare no competing interests.
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