A high-sensitive HMab-2 specifically detects IDH1-R132H, the most common IDH mutation in gliomas

作者:Fujii Yuki; Ogasawara Satoshi; Oki Hiroharu; Liu Xing; Kaneko Mika K; Takano Shingo; Kato Yukinari*
来源:Biochemical and Biophysical Research Communications, 2015, 466(4): 733-739.
DOI:10.1016/j.bbrc.2015.09.070

摘要

Isocitrate dehydrogenase 1 (IDH1) mutations have been detected in gliomas and other tumors. Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). Several monoclonal antibodies (mAbs) specific for IDH1 mutations have been established, such as H09, IMab-1, and HMab-1 against IDH1-R132H, which is the most frequent IDH1 mutation in gliomas. In this study, we established a novel high-sensitive mAb HMab-2, which reacts with IDH1-R132H but not with wild type IDH1 in ELISA. HMab-2 reacted only with IDH1-R132H, not with wild type IDH1/2 and other IDH1/2 mutants in Western-blot analysis. Furthermore, HMab-2 recognized IDH1-R132H more sensitively compared with our previously established HMab-1. HMab-2 detected endogenous IDH1-R132H protein expressed in glioblastoma in immunohistochemical analysis. HMab-2 is expected to be useful for the diagnosis of IDH1-R132H-bearing tumors.

  • 出版日期2015-10-30