TY - JOUR
T1 - A high-sensitive HMab-2 specifically detects IDH1-R132H, the most common IDH mutation in gliomas
AU - Fujii, Yuki
AU - Ogasawara, Satoshi
AU - Oki, Hiroharu
AU - Liu, Xing
AU - Kaneko, Mika K.
AU - Takano, Shingo
AU - Kato, Yukinari
PY - 2015/10/30
Y1 - 2015/10/30
N2 - Isocitrate dehydrogenase 1 (IDH1) mutations have been detected in gliomas and other tumors. Although IDH1 catalyzes the oxidative carboxylation of isocitrate to α-ketoglutarate (α-KG) in cytosol, mutated IDH1 proteins possess the ability to change α-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.
AB - Isocitrate dehydrogenase 1 (IDH1) mutations have been detected in gliomas and other tumors. Although IDH1 catalyzes the oxidative carboxylation of isocitrate to α-ketoglutarate (α-KG) in cytosol, mutated IDH1 proteins possess the ability to change α-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.
KW - HMab-2
KW - IDH1
KW - IDH1 mutation
KW - Monoclonal antibody
KW - R132H
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U2 - 10.1016/j.bbrc.2015.09.070
DO - 10.1016/j.bbrc.2015.09.070
M3 - Article
C2 - 26381180
AN - SCOPUS:84943235753
VL - 466
SP - 733
EP - 739
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -