Gene affected:
IDH1 and IDH2: isocitrate dehydrogenase 1 and 2 (NM_005896.2 and NM_002168.2)

Clinical significance
Mutations affecting IDH1 or IDH2 occur predominantly in association with normal karyotype AML; the prognostic significance is greatly influenced by co-occurring mutation and so remains unclear at this time.

Function of gene

IDH1 and IDH2 mediate the conversion of isocitrate to alpha-ketoglutarate. Clinically significant mutations affecting the IDH genes cause a gain of function for the proteins they encode. This gain in function generates 2-hydroxyglutarate which inhibits proteins involved in epigenetic regulation. The effect of these mutations is to cause DNA and histone hypermethylation and cause the altered expression of genes (include TET2) resulting in impaired hematopoietic differentiation. In AML, IDH1 mutations most often involve R132. In IDH2, mutations affecting R140 represent ~80% of incidence in AML whereas IDH2 R172 mutations appear to be more frequent in older patients.

NGS panel gene coverage

The NGS panel detects the gain of function mutations that affect exon 4 of IDH1 and IDH2 that are associated with malignant transformation.


AML: (around 20%)
MDS (5% of cases)
Most often normal karyotype
Mutation affecting IDH2 is more frequent.
While several studies have suggested that IDH1 or IDH2 mutations cause adverse outcome, other studies have reported no clear effect, and in some cases an improved survival.

Associated genetic features:

1. IDH1 and IDH2 mutations frequently occur in conjunction with NPM1 or FLT3-ITD mutations

2. IDH1 and IDH2 mutations are almost always mutually exclusive with TET2 and WT1 mutations


GeneWiki link:
Gene Wiki entry for IDH1
Gene Wiki entry for IDH2

1. General reference 1
2. General reference 2