What is the IDH1 and IDH2 mutation?
What is the IDH1 and IDH2 mutation?
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas and secondary glioblastomas, chondrosarcomas, intrahepatic cholangiocarcinomas, and hematologic malignancies.
What is an IDH1 mutation?
It is now clear that mutations in IDH1 and IDH2 are driver mutations in low grade gliomas, likely through 2-HG production. These mutations lead to a hypermethylation phenotype as well as changes in cellular metabolism and response to hypoxic and oxidative stress.
What is IDH2 mutation?
The IDH2 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. These mutations change single protein building blocks (amino acids) in the isocitrate dehydrogenase 2 enzyme.
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.
What is IDH1 inhibitor?
Ivosidenib is the first approved oral, targeted, small-molecule inhibitor of the isocitrate dehydrogenase 1 (IDH1) mutation seen in AML. IDH1 mutations have been associated with significantly worse outcomes in disease-free survival, relapse-free survival, and overall survival (NCCN, 2018).
What is IDH wild type?
IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature.
What does IDH wildtype mean?
IDH ‘wild’ type status – This occurs in about 90% of GBM brain tumours and usually indicates that the tumour formed as glioblastoma since the very beginning (primary GBM) and carries a worse prognosis than those classified as being IDH mutant.
What chromosome is IDH2?
Isocitrate dehydrogenase [NADP], mitochondrial is an enzyme that in humans is encoded by the IDH2 gene….
| IDH2 | ||
|---|---|---|
| RefSeq (protein) | NP_001276839 NP_001277043 NP_002159 | NP_766599 |
| Location (UCSC) | Chr 15: 90.08 – 90.1 Mb | Chr 7: 80.09 – 80.12 Mb |
| PubMed search | ||
| Wikidata |
What is IDH1 wild-type?
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 do Hypomethylating agents do?
A hypomethylating agent (or demethylating agent) is a drug that inhibits DNA methylation. Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, hypomethylating agents are considered a type of epigenetic therapy.
What is Vorasidenib?
Vorasidenib, an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes, is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma (NCT04164901).
What is IDH wildtype glioblastoma?
What are the effects of IDH1 and IDH2 mutations in tumorigenesis?
Mutations targeting IDH1 and IDH2 result in simultaneous loss of their normal catalytic activity, the production of α-ketoglutarate (α-KG), and gain of a new function, the p … IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives
What do we know about the IDH1 gene?
A mutation in the isocitrate dehydrogenase 1 ( IDH1) gene was first discovered during a sequencing effort across colorectal cancers ( Sjöblom et al., 2006 ). More recently, somatic mutations in IDH1 were identified through a genome wide mutation analysis in glioblastoma ( Parsons et al., 2008 ).
Which histologic findings are characteristic of IDH1 gliomas?
In lower grade gliomas with a high percentage of IDH mutation, differences in other tumor mutations and copy number alterations have been found associated with histologic subtypes. IDH1 mutations often occur with a TP53 mutation in astrocytic tumors, and these tumors rarely demonstrate loss of chromosomes 1p and 19q.
Is IDH mutation a driver of tumor initiation in glioblastomas?
While commonly seen with alterations associated with low grade glioma, IDH mutation is rarely observed with genetic alterations commonly seen in high frequency in primary GBMs (e.g., EGFR), supporting the idea that IDH mutation is not a driver of tumor initiation in these GBM subtypes .
