|Transcript ID (GRCh37/hg19)||ENST00000330062|
|Genomic Coordinates (GRCh37/hg19)||15:90631837-90631839|
|Tumor Type||Primary Site|
IDH2 is a mitochondrial enzyme involved in citrate metabolism. Mutations at Arg140 and Arg172 of IDH2 are typically heterozygous mutations and considered gain of function mutations that lead to increased levels of 2-hydroxyglutarate which is believed to alter epigenetic regulation (ie, DNA methylation) in AML. Mutations of IDH2 appear to be mutually exclusive of mutations in TET2, another gene involved in regulation of DNA methylation, and also exclusive of mutations in IDH1. Mutations of IDH2 have been shown to lead to increased DNA methylation in AML. IDH2 mutations have been reported in 10-20% of AML and are often associated with a normal karyotype. IDH2 mutations have been reported in less than 5% of cases of MDS and less than 10% of myeloproliferative neoplasms. The prognostic impact of IDH2 mutations in AML appears uncertain due to conflicting reports. In the setting of essential thrombocytosis, primary myelofibrosis and MDS, the presence of IDH2 mutations is associated with reduced survival. Therapeutic targeting with an FDA approved mutant IDH2 inhibitor (enasidenib (AG-221)) has been reported for patients with relapsed or refractory IDH2-mutated AML.
IDH2 R172X mutations have been detected in 55-82% of sinonasal undifferentiated carcinomas (SNUC). These tumors may be amenable to IDH2-targeted therapies.