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IDH2
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IDH2 R140Q
GeneIDH2
Variantmissense
Amino Acid ChangeR140Q
Transcript ID (GRCh37/hg19)ENST00000330062
Codon140
Exon4
Germline/Somatic?Somatic
Pertinent Negative In
Tumor TypePrimary Site
See All Pertinent Negatives

Interpretations

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Tier 1
IDH2
Variants
IDH2 R140Q
IDH2 R172K
IDH2 codon(s) 140, 172 any
Primary Sites
Spinal Cord
Brain
Brain, Supratentorial
Brain, Infratentorial
Tumor Types
Glioblastoma
Astrocytoma, Anaplastic
Ependymoma
Oligodendroglioma
Interpretation

IDH1 or IDH2 mutations are found in >70% of lower grade diffusely infiltrative gliomas and in >90% of secondary glioblastoma. IDH mutational status has been reported to be a favorable prognostic indicator relative to wild-type gliomas of similar histology, regardless of grade. Therapeutic strategies exploiting mutated IDH protein, including through direct inhibition and vaccine-based approaches, are currently the subject of preclinical research and clinical trials.

Last updated: 2017-01-20 03:26:51 UTC
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Tier 1
IDH2
Variants
IDH2 R140Q
IDH2 R172K
IDH2 codon(s) 140, 172 any
IDH2 codon(s) 140 missense
IDH2 codon(s) 172 missense
Primary Sites
Blood
Bone Marrow
Tumor Types
Myeloproliferative Neoplasm
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Primary Myelofibrosis
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

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.

Last updated: 2018-11-12 20:41:32 UTC
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Tier 2
IDH2
Variants
IDH2 R140Q
IDH2 codon(s) 140, 172 any
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Squamous Cell Carcinoma
Non-Small Cell Lung Carcinoma
Interpretation

IDH2 is a mitochondrial enzyme involved in citrate metabolism. Mutations at Arg140 and Arg172 of IDH2 are typically heterozygous and are considered gain-of-function mutations that lead to increased levels of 2-hydroxyglutarate believed to alter epigenetic regulation in various tumors, especially in myeloid neoplasms. The Arg140 mutation of IDH2 has not been reported previously in lung tumors. However, a few other IDH2 mutations have been described in non-small cell lung cancers (NSCLC) in a very small number of patients in the literature. The prognostic impact of IDH2 mutations in NSCLC remains uncertain at this time. Mutant IDH2 may provide a potential therapeutic target in some settings. Clinical correlation is recommended.

Last updated: 2016-06-25 19:44:17 UTC
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Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


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