A monoclonal antibody IMab-1 specifically recognizes IDH1{sup R132H}, the most common glioma-derived mutation
- Department of Pathology, Duke University Medical Center, DUMC-3156, Durham, NC 27710 (United States)
IDH1 (isocitrate dehydrogenase 1) mutations have been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas as well as secondary glioblastomas. In contrast, primary glioblastomas very rarely contain IDH1 mutations, although primary and secondary glioblastomas are histologically indistinguishable. The IDH1 mutations are remarkably specific to a single codon in the conserved and functionally important Arg132 in IDH1. In gliomas, the most frequent IDH1 mutations (>90%) were G395A (R132H). In this study, we immunized mice with R132H-containing IDH1 (IDH1{sup R132H}) peptide. After cell fusion using Sendai virus envelope, the monoclonal antibodies (mAbs), which specifically reacted with IDH1{sup R132H}, were screened in ELISA. One of the mAbs, IMab-1 reacted with the IDH1{sup R132H} peptide, but not with wild type IDH1 (IDH1{sup wt}) peptide in ELISA. In Western-blot analysis, IMab-1 reacted with only the IDH1{sup R132H} protein, not IDH1{sup wt} protein or the other IDH1 mutants, indicating that IMab-1 is IDH1{sup R132H}-specific. Furthermore, IMab-1 specifically stained the IDH1{sup R132H}-expressing cells in astrocytomas in immunohistochemistry, whereas it did not react with IDH1{sup R132H}-negative primary glioblastoma sections. In conclusion, we established an anti-IDH1{sup R132H}-specific monoclonal antibody IMab-1, which should be significantly useful for diagnosis and biological evaluation of mutation-bearing gliomas.
- OSTI ID:
- 22199911
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 390, Issue 3; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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