Metabolic syndromes and malignant transformation: where the twain shall meet.
Recurrent somatic mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes that result in the accumulation of D-2-hydroxyglutarate (D-2-HG) have been identified in malignant gliomas and in acute myeloid leukemia (AML). However, the function of this metabolite in normal and malignant tissues remains uncertain. A report in the current issue of Science describes a germline IDH2 mutation in a subset of patients with a rare metabolic disorder--D-2-hydroxyglutaric aciduria-that is similar to mutations seen in cancer patients. These observations further elucidate the effects of IDH mutations on normal and malignant cells.
Bhagwat
Neha
N
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Levine
Ross L
RL
D002471:Cell Transformation, Neoplastic; D005910:Glioma / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D009154:Mutation
D005977:Glutarates; C019417:alpha-hydroxyglutarate; D007521:Isocitrate Dehydrogenase