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Published in:

01-01-2015 | Review Article

Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas

Author: Yukinari Kato

Published in: Brain Tumor Pathology | Issue 1/2015

Abstract

Mutations of isocitrate dehydrogenase 1/2 (IDH1/2) have been reported in gliomas and other types of tumors, such as acute myeloid leukemias, cartilaginous tumors, intrahepatic cholangiocarcinomas, osteosarcomas, and giant cell tumors of bone. In gliomas, IDH mutations uniformly occur in the functionally critical arginine 132 residue (R132) of IDH1 and arginine 172 residue (R172) of IDH2. IDH1 and IDH2 catalyze the oxidative carboxylation of isocitrate to α-ketoglutarate (α-KG) in the cytosol and mitochondria, respectively. In contrast, mutated IDH1/2 proteins possess a neomorphic enzymatic function that changes α-KG into the oncometabolite, R(–)-2-hydroxyglutarate, resulting in genomic hypermethylation, histone methylation, genetic instability, and malignant transformation. To date, several monoclonal antibodies (mAbs) specific for IDH1/2 mutations such as anti-IDH1-R132H mAbs (clone H09, clone IMab-1, and clone HMab-1) or an anti-IDH1-R132S mAb (clone SMab-1) have been established. Furthermore, one of multi-specific mAbs, MsMab-1, recognizes IDH1 mutants (R132H, R132S, R132G) and IDH2 mutants (R172S, R172G), which are observed in gliomas. Another mAb, MsMab-2, recognizes IDH1-R132L and IDH2-R172M. These IDH1/2 mutation-specific mAbs are useful for the immunohistochemical determination of IDH1/2 mutation-bearing gliomas.

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Title: Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas
Author: Yukinari Kato
Publication date: 01-01-2015
Publisher: Springer Japan
Published in: Brain Tumor Pathology / Issue 1/2015
Print ISSN: 1433-7398
Electronic ISSN: 1861-387X
DOI: https://doi.org/10.1007/s10014-014-0202-4

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Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas

Abstract

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Abstract

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