|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The discovery of somatic mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone event in cancer biology.
|
20972461 |
2010 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.
|
20368543 |
2010 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
IDH1 and IDH2 mutations are usually heterozygous in cancer, and they appear to confer a neomorphic enzyme activity for the enzymes to catalyze the production of D-2-hydroxyglutarate.
|
20513808 |
2010 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
This review surveys the prevalence of IDH mutations in cancer and explores current mechanistic understanding of IDH mutations with implications for diagnostic and therapeutic development for the treatment of gliomas and AML.
|
20692206 |
2010 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The fact that the gain of the enzymatic activity to produce 2HG is a shared feature of the IDH1 and IDH2 mutations suggests that this is an important function for these mutants in driving cancer pathogenesis.
|
21326614 |
2011 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
A recent cancer genome-sequencing project revealed that more than 70% of low-grade gliomas bear mutations in one of two NAD(+)-dependent isocitrate dehydrogenase enzymes, namely, IDH1 and IDH2.
|
21284999 |
2011 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Therefore, the authors investigated NADPH-producing dehydrogenases using in silico analysis of human cancer gene expression microarray data sets and metabolic mapping of human and rodent tissues to determine the role of IDH in total NADPH production.
|
21527585 |
2011 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy.
|
22980977 |
2012 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These data broaden our understanding of how IDH mutations may contribute to cancer through either neomorphic R(-)-2HG production or reduced wild-type enzymatic activity, and highlight the potential value of metabolite screening in identifying IDH-mutated tumors associated with elevated oncometabolite levels.
|
21996744 |
2012 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The understanding that oncogenes can have profound effects on cellular metabolism and the discovery of mutations and alterations in several metabolism-related enzymes--isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), succinate dehydrogenase (SDH), fumarate hydratase (FH), and pyruvate kinase M2 (PKM2)--has renewed interest in cancer metabolism and renewed hope of taking therapeutic advantage of cancer metabolism.
|
23071355 |
2012 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Genes encoding for isocitrate dehydrogenases 1 and 2, IDH1 and IDH2, are frequently mutated in multiple types of human cancer.
|
23071358 |
2012 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
IDH1 and IDH2 with cancer-associated mutations at the active site arginines were unable to carry out the reductive carboxylation of αKG.
|
22442146 |
2012 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
We examined IDH1 R132 and IDH2 R140/R172 mutations by high resolution melting analysis and direct sequencing in Chinese patients with different myeloid malignancies including 198 acute myeloid leukemia (AML), 82 myelodysplastic syndrome (MDS), 85 chronic myeloid leukemia, and 57 myeloproliferative neoplasms.
|
21997850 |
2012 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These data provide proof-of-concept that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer.
|
23558173 |
2013 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Therefore, we studied the effect of TAT-IDP(S) in a more heterogeneous Bcl-2-dependent cancer model using a set of 'primed to death' diffuse large B-cell lymphoma (DL-BCL) cell lines containing elevated Bcl-2 levels.
|
23681227 |
2013 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Mutation in the IDH1 or IDH2 genes occurs frequently in gliomas and other human malignancies.
|
24077826 |
2013 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Here we review what is known about the molecular mechanisms of transformation by mutant IDH and discuss their implications for the development of targeted therapies to treat IDH mutant malignancies.
|
23630074 |
2013 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Novel multiplex bead-based assay for detection of IDH1 and IDH2 mutations in myeloid malignancies.
|
24098815 |
2013 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Despite the prospect of treating AML and other cancers by targeting IDH mutant proteins, it remains unclear how these mutants affect tumor development and maintenance in vivo, and no cancer models exist to study the action of IDH2 mutants in vivo.
|
24065765 |
2013 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
This knowledge provides a conceptual foundation for understanding how mutations in the metabolic enzymes SDH, FH, and IDH can result in cancer and, more broadly, for how alterations in metabolism and nutrition might contribute to disease.
|
23540690 |
2013 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple αKG-dependent dioxygenases, and results in alterations in cell differentiation, survival, and extracellular matrix maturation.
|
25043045 |
2014 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Hence, we propose the TCM compounds, precatorine and abrine, as potential candidates as lead compounds for further study in drug development process with the IDH2 R140Q mutant protein against cancer.
|
24995286 |
2014 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
An intriguing aspect of IDH-mutant tumors is the aberrant production and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which may play a pivotal oncogenic role in these malignancies.
|
24760710 |
2014 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These tumors are characterized by frequent gain-of-function mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes-that are also common in subsets of neural, haematopoietic and bone tumors, but rare or absent in the other types of gastrointestinal malignancy.
|
25485496 |
2014 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies.
|
24699305 |
2014 |