Abstract
Glioblastoma is the most fatal brain cancer found in humans. Patients suffering from glioblastoma have a dismal prognosis, with a median survival of 15 months. The tumor may develop rapidly de novo in older patients or through progression from anaplastic astrocytomas in younger patients if glioblastoma is primary or secondary, respectively. During the past decade, significant advances have been made in the understanding of processes leading to glioblastoma, and several important genetic defects that appear to be important for the development and progression of this tumor have been identified. Particularly, the discovery of recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) gene has shed new light on the molecular landscape in glioblastoma. Indeed, emerging research on the consequences of mutant IDH1 protein expression suggests that its neomorphic enzymatic activity catalyzing the production of the oncometabolite 2-hydroxyglutarate influences a range of cellular programs that affect the epigenome and contribute to glioblastoma development. One of the exciting observations is the presence of IDH1 mutation in the vast majority of secondary glioblastoma, while it is almost absent in primary glioblastoma. Growing data indicate that this particular mutation has clinical and prognostic importance and will become a critical early distinction in diagnosis of glioblastoma.
Highlights
Glioblastoma is the most common brain malignancy and one of the most aggressive cancers found in humans
Extensive research has been performed to determine the prognostic value of isocitrate dehydrogenase 1 (IDH1) mutations, and a better prognosis has been generally reported in glioblastoma patients carrying an IDH1 mutation
The best known example is the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation and response to alkylating agents, but there is the gene suppressor of cytokine signaling 1 (SOCS1), which in some glioblastomas enhanced resistance to ionizing radiation and decreased activation of MAPKs associated with the ERK pathway after transcriptional silencing by hypermethylation [58]
Summary
Glioblastoma is the most common brain malignancy and one of the most aggressive cancers found in humans It is divided into primary and secondary types. Primary glioblastoma manifests rapidly de novo without recognizable precursor lesions, and is by far the more common, accounting for 80% of cases It predominates in elderly patients and is characterized by rapid progression and short survival time. Secondary glioblastoma evolves from lower-grade gliomas, such as grade II diffuse astrocytoma or grade II anaplastic astrocytoma, and is typically seen in younger patients It can be diagnosed with clinical or histological evidence [1]. One of the most exciting and clinically relevant observations was the discovery that a high percentage of secondary glioblastomas and a very small percentage of primary glioblastoma harbor mutations in the isocitrate dehydrogenase 1 (IDH1) gene. The review presents a brief overview on mutations commonly found in glioblastoma, and prunes the consequences of IDH1 mutation on glioblastoma biology to better understand the potential role of this particular mutation in the development of this tumor
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