Recent findings on molecular alterations in IDH1, TP53, and CASP9 in gliomagenesis

Abstract

Isocitrate dehydrogenase (IDH) mutations have been the focus of glioma-related neuroscience research since the discovery of the gene in 2008. IDH1 has been identified as a key enzyme in cellular metabolism, epigenetic regulation, redox regulation, and DNA repair and is thought to be one of the most important factors in gliomagenesis. IDH1 mutations cause neomorphic activity, resulting in an increase in 2-hydroxyglutarate production and a decrease in NADPH production. Emerging research has identified IDH1 mutations in the vast majority of low-grade gliomas and secondary glioblastomas, but these mutations are extremely uncommon in primary glioblastomas. Other genetic defects appear to play a significant role in glioma initiation and progression. In this study, we review recent findings on oncogenic alterations in IDH1, TP53, and CASP9 to identify any potential molecular correlations and interrelationships that lead to gliomagenesis. The roles and molecular interactions of these glioma-associated genes in gliomagenesis are elucidated. In addition, we highlight studies on stem cell modeling in glioma-associated genetic alterations that have been conducted over the past several decades.