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C-terminally truncated form of αB-crystallin is associated with IDH1 R132H mutation in anaplastic astrocytoma

Journal of Neuro-Oncology volume 117, pages 53–65 (2014)Cite this article

Abstract

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 IDH1R132H mutant and wild type anaplastic (grade III) astrocytoma from human brain cancer tissues. We show that expression levels of many proteins are altered in IDH1R132H 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 IDH1R132H 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 IDH1R132H mutation. In conclusion, the association of a C-terminally truncated form of αB-crystallin protein with the IDH1R132H mutation is a novel finding that could impact apoptosis and stress response in IDH1 mutant glioma.

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Acknowledgments

We thank Sergey Mareninov, Ryan W. Wilson, Desiree Sanchez and Gregory M. Lucey (UCLA Department of Pathology and Laboratory Medicine) for technical support with immunohistochemistry and immunoblotting.

Conflict of interest

None of the authors has any financial or other conflicts of interest that might raise the question of bias in this work.

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Author notes

  1. Leili Mirsadraei

    Present address: Department of Pathology, University of California San Diego Medical Center, 200 W Arbor Dr., MC 8320, San Diego, CA, 92103, USA

Affiliations

  1. Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA, 90095, USA

    Kavitha S. Rajavel, Lea Guo, Michael Linetsky & Whitney B. Pope

  2. Department of Biological Chemistry, David Geffen School of Medicine at UCLA, 615 Charles E. Young Dr. South, Los Angeles, CA, 90095, USA

    Nuraly K. Avliyakulov, Khanh Minh T. Le & Michael J. Haykinson

  3. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 18-161 CHS, Los Angeles, CA, 90095, USA

    Leili Mirsadraei & William H. Yong

  4. Department of Neurosurgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA

    Linda M. Liau

  5. Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Reed 1-230, Los Angeles, CA, 90230, USA

    Sichen Li, Albert Lai, Phioanh L. Nghiemphu & Timothy F. Cloughesy

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  1. Nuraly K. Avliyakulov
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Corresponding author

Correspondence to Whitney B. Pope.

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Avliyakulov, N.K., Rajavel, K.S., Le, K.M.T. et al. C-terminally truncated form of αB-crystallin is associated with IDH1 R132H mutation in anaplastic astrocytoma. J Neurooncol 117, 53–65 (2014). https://doi.org/10.1007/s11060-014-1371-z

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  • DOI: https://doi.org/10.1007/s11060-014-1371-z

Keywords

  • IDH1 mutation
  • Glioma
  • Astrocytoma
  • Proteomics
  • 2D DIGE
  • C-terminally truncated form of αB-crystallin protein