Work

From genomics to the clinic: biological and translational insights of mutant IDH1/2 in glioma

Year: 2013

Type: article

Abstract: The characterization of the genomic alterations across all human cancers is changing the way that malignant disease is defined and treated. This paradigm is extending to glioma, where the discovery of recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) gene has shed new light on the molecular landscape in glioma and other IDH-mutant cancers. The IDH1 mutations are present in the vast majority of low-grade gliomas and secondary glioblastomas. Rapidly emerging work 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, transcriptional programs, hypoxia-inducible factor biology, and development. In the brief time since its discovery, knowledge of the IDH mutation status has had significant translational implications, and diagnostic tools are being used to monitor its expression and function. The concept of IDH1-mutant versus IDH1-wild type will become a critical early distinction in diagnostic and treatment algorithms.

Source: Neurosurgical FOCUS

DOI: 10.3171/2012.12.focus12355

Authors: Gavin P. Dunn, Ovidiu C. Andronesi, Daniel P. Cahill

Institutions: Harvard University, Massachusetts General Hospital

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences