Large Scale Identification of Variant Proteins in Glioma Stem Cells

Ekaterina Mostovenko, Ákos Végvári, Melinda Rezeli, Cheryl F. Lichti, David Fenyö, Qianghu Wang, Frederick F. Lang, Erik P. Sulman, K. Barbara Sahlin, György Marko-Varga, Carol L. Nilsson

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Glioblastoma (GBM), the most malignant of primary brain tumors, is a devastating and deadly disease, with a median survival of 14 months from diagnosis, despite standard regimens of radical brain tumor surgery, maximal safe radiation, and concomitant chemotherapy. GBM tumors nearly always re-emerge after initial treatment and frequently display resistance to current treatments. One theory that may explain GBM re-emergence is the existence of glioma stemlike cells (GSCs). We sought to identify variant protein features expressed in low passage GSCs derived from patient tumors. To this end, we developed a proteomic database that reflected variant and nonvariant sequences in the human proteome, and applied a novel retrograde proteomic workflow, to identify and validate the expression of 126 protein variants in 33 glioma stem cell strains. These newly identified proteins may harbor a subset of novel protein targets for future development of GBM therapy.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalACS Chemical Neuroscience
Volume9
Issue number1
DOIs
StatePublished - Jan 17 2018
Externally publishedYes

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Keywords

  • bioinformatics
  • GBM
  • Glioblastoma
  • parallel reaction monitoring
  • precision medicine
  • protein quantification
  • protein single amino acid variants
  • proteomics
  • targeted mass spectrometry
  • transcriptomics

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Cite this

Mostovenko, E., Végvári, Á., Rezeli, M., Lichti, C. F., Fenyö, D., Wang, Q., Lang, F. F., Sulman, E. P., Sahlin, K. B., Marko-Varga, G., & Nilsson, C. L. (2018). Large Scale Identification of Variant Proteins in Glioma Stem Cells. ACS Chemical Neuroscience, 9(1), 73-79. https://doi.org/10.1021/acschemneuro.7b00362