Malignant gliomas are the most common human
primary brain tumors. Point mutation of
amino acid arginine 132 to
histidine (R132H) in the IDH1
protein leads to an enzymatic gain-of-function and is thought to promote gliomagenesis. Little is known about the downstream effects of the IDH1 mutation on
protein expression and how and whether changes in
protein expression are involved in
tumor formation or propagation. In the current study, we used 2D DIGE (difference gel electrophoresis) and mass spectrometry to analyze differences in
protein expression between IDH1(R132H) mutant and wild type anaplastic (
grade III) astrocytoma from human
brain cancer tissues. We show that expression levels of many
proteins are altered in IDH1(R132H) mutant
anaplastic astrocytoma. Some of the most over-expressed
proteins in the mutants include several forms of αB-
crystallin, a small heat-shock and
anti-apoptotic protein. αB-
crystallin proteins are elevated up to 22-fold in IDH1(R132H) mutant
tumors, and αB-
crystallin expression appears to be controlled at the post-translational level. We identified the most abundant form of αB-
crystallin as a low molecular weight species that is C-terminally truncated. We also found that overexpression of αB-
crystallin can be induced by transfecting U251 human
glioblastoma cell lines with the IDH1(R132H) mutation. In conclusion, the association of a C-terminally truncated form of αB-
crystallin protein with the IDH1(R132H) mutation is a novel finding that could impact apoptosis and stress response in IDH1 mutant
glioma.