What is IDH1-R132H?

IDH1R132H is a gain-of-function mutation that converts α-ketoglutarate to (R)-2-hydroxyglutarate (2HG) (9–11). 2HG inhibits DNA and histone demethylases, namely the ten-eleven translocation enzymes and lysine demethylases, respectively, resulting in hypermethylation of DNA and histones (10, 11).

What does IDH1-R132H negative mean?

In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM.

What is IDH1?

The IDH1 gene provides instructions for making an enzyme called isocitrate dehydrogenase 1. This enzyme is primarily found in the fluid-filled space inside cells (the cytoplasm). It is also found in cellular structures called peroxisomes, which are small sacs within cells that process many types of molecules.

What does IDH1 wild type mean?

As a reversible dehydrogenase, wild-type IDH1 is a homodimeric enzyme that reversibly catalyzes isocitrate into α-KG accompanied with the generation of NADPH from NADP+ in cytosol, which has been proven to be physiologically crucial in the metabolism of lipids, amino acids, and sugars in cells.

What is IDH in tumors?

Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma.

What is an IDH inhibitor?

IDH inhibitors alter the activity of IDH enzymes, resulting in reduction of α-ketoglutarate (KG) to D-2-hydroxyglutarate (2-HG), a competitive inhibitor of α-KG. From: Pharmacoepigenetics, 2019.

Why is IDH important?

Isocitrate dehydrogenase (IDH) enzymes, of which there are three isoforms, are essential enzymes that participate in several major metabolic processes, such as the Krebs cycle, glutamine metabolism, lipogenesis and redox regulation.

What is the difference between IDH1 and IDH2?

Although IDH1 and IDH2 are highly similar and catalyze identical reactions, IDH1 is localized in the cytosol and IDH2 is found in the mitochondrial matrix. In addition, the spectrum of cancers and their subtypes are different.