RT Journal Article
SR Electronic
T1 Glioma CpG Island Methylator Phenotype (G-CIMP): Biological and Clinical Implications
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 169680
DO 10.1101/169680
A1 Tathiane M Malta
A1 Camila F de Souza
A1 Thais S Sabedot
A1 Tiago C Silva
A1 Maritza QS Mosella
A1 Steven N Kalkanis
A1 James Snyder
A1 Ana Valeria B Castro
A1 Houtan Noushmehr
YR 2017
UL http://biorxiv.org/content/early/2017/07/28/169680.abstract
AB Gliomas are a heterogenous 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 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 genotypic and phenotypic features, thereby narrowing defined subgroups. The new classification recommends the molecular diagnosis of IDH mutational status in gliomas. IDH-mutant gliomas are prompt to 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) provided a further refinement in glioma classification that is independent of grade and histology. This scheme is useful for predicting patient outcome and may be translated into effective therapeutic strategies tailored to each patient. In the present review, we highlight the evolution of our understanding of G-CIMP subsets and how recent advances in characterizing gliomas’ genome and epigenome may influence future basic and translational research.2-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))MGMTO6-methyl-guanine DNA methyltransferaseNADNicotinamide adenine dinucleotideOSOverall survivalTMZTemozolomideWHOWorld Health Organization2-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))MGMTO6-methyl-guanine DNA methyltransferaseNADNicotinamide adenine dinucleotideOSOverall survivalTMZTemozolomideWHOWorld Health Organization