TY - JOUR T1 - Glioma CpG Island Methylator Phenotype (G-CIMP): Biological and Clinical Implications JF - bioRxiv DO - 10.1101/169680 SP - 169680 AU - Tathiane M Malta AU - Camila F de Souza AU - Thais S Sabedot AU - Tiago C Silva AU - Maritza QS Mosella AU - Steven N Kalkanis AU - James Snyder AU - Ana Valeria B Castro AU - Houtan Noushmehr Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/09/14/169680.abstract N2 - Gliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties. Despite advances in surgical techniques and clinical regimens, treatment of high-grade glioma remains challenging and carries dismal rates of therapeutic success and overall survival. Challenges include the molecular complexity of gliomas, as well as inconsistencies in histopathological grading, resulting in an inaccurate prediction of disease progression and failure in the use of standard therapy. The updated 2016 World Health Organization (WHO) classification of tumors of the central nervous system reflects a refinement of tumor diagnostics by integrating the genotypic and phenotypic features, thereby narrowing the defined subgroups. The new classification recommends the molecular diagnosis of the IDH mutational status in gliomas. IDH-mutant gliomas manifest the CpG Island Methylator Phenotype (G-CIMP). Notably, the recent identification of clinically relevant subsets of G-CIMP tumors (G-CIMP-high and G-CIMP-low) provide a further refinement in glioma classification that is independent of grade and histology. This scheme may be useful for predicting patient outcome and may be translated into effective therapeutic strategies tailored to each patient. In this review, we highlight the evolution of our understanding of the G-CIMP subsets and how recent advances in characterizing the genome and epigenome of gliomas may influence future basic and translational research.Conflict of interest: The authors declare no conflict of interestABBREVIATIONS2-HG2-hydroxyglutarate (2-HG)α-KGα-ketoglutarateCNSCentral nervous systemCGICpG IslandCpG5'-C-phosphate-G-3'CTCFCCCTC-binding factorG-CIMPGlioma CpG island methylator phenotypeGBMGlioblastoma (World Health Organization grade IV)GWASGenome-wide association studyHDACHistone deacetylaseIDHIsocitrate dehydrogenaseLGGLower-grade glioma (here defined by diffusely infiltrative low-grade or intermediate-grade glioma (World Health Organization grade II or III))MGMTO-6-methylguanine DNA methyltransferaseNADNicotinamide adenine dinucleotideOSOverall survivalTMZTemozolomideWHOWorld Health Organization ER -