Molecular and prognostic features of IDH/BRAF/H3F3A-wild type young adult glioblastomas

Summary In this study, we have been focused on investigations of glioblastomas in young adults aged 19 to 44 years. Objective. In the current study, we aimed to stratify an IDH/BRAF/H3F3A wild-type young adult glioblastoma cohort assessed through genome-wide molecular profiling. Materials and methods. Using genome-wide DNA methylation and hierarchical clustering, we have investigated a representative cohort of homogeneously treated primary 91 glioblastomas. All tumors were considered wild-type young adult glioblastomas because they showed no mutations of IDH/BRAF/H3F3A genes. 64 Results. Two molecular clusters have been identified that will be essential for rational stratification of wild-type young adult glioblastomas in clinical trials and for guiding optimal targeted therapeutic regimes. Conclusion. The study demonstrates the molecular heterogeneity of IDH/BRAF/H3F3A wild-type young adult glioblastomas, as detected by global DNA methylation analyses. The recognition of two molecular subgroups of wild-type young adult glioblastomas also revealed close correlations with biological parameters and clinical outcomes that may be predictive of response to standard treatment protocols and also could be useful for definition of molecular-based therapy. However, it should be recommended, in a routine diagnosis of glioblastomas, screen mutations of the IDH1/2, BRAF, H3F3A, TERT, TP53, ATRX by direct sequencing, and MGMT methylation status.