Proteomic profiling of high risk medulloblastoma reveals functional biology

Jerome A. Staal, Ling San Lau, Huizhen Zhang, Wendy J. Ingram, Andrew R. Hallahan, Paul A. Northcott, Stefan M. Pfister, Robert J. Wechsler-Reya, Jessica M. Rusert, Michael D. Taylor, Yoon-Jae Cho, Roger J. Packer, Kristy J. Brown, Brian R. Rood

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior.

Original languageEnglish (US)
Pages (from-to)14584-14595
Number of pages12
JournalOncotarget
Volume6
Issue number16
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Medulloblastoma
Proteomics
Neoplasms
Proteome
Proteins
Biological Phenomena
Pyruvate Kinase
Ribonucleoproteins
Alternative Splicing
Metabolic Networks and Pathways
Isotopes
Molecular Biology
Mass Spectrometry

Keywords

  • Cancer
  • cMYC
  • Glycolysis
  • Medulloblastoma
  • Proteomics

ASJC Scopus subject areas

  • Oncology

Cite this

Staal, J. A., Lau, L. S., Zhang, H., Ingram, W. J., Hallahan, A. R., Northcott, P. A., ... Rood, B. R. (2015). Proteomic profiling of high risk medulloblastoma reveals functional biology. Oncotarget, 6(16), 14584-14595. https://doi.org/10.18632/oncotarget.3927

Proteomic profiling of high risk medulloblastoma reveals functional biology. / Staal, Jerome A.; Lau, Ling San; Zhang, Huizhen; Ingram, Wendy J.; Hallahan, Andrew R.; Northcott, Paul A.; Pfister, Stefan M.; Wechsler-Reya, Robert J.; Rusert, Jessica M.; Taylor, Michael D.; Cho, Yoon-Jae; Packer, Roger J.; Brown, Kristy J.; Rood, Brian R.

In: Oncotarget, Vol. 6, No. 16, 01.01.2015, p. 14584-14595.

Research output: Contribution to journalArticle

Staal, JA, Lau, LS, Zhang, H, Ingram, WJ, Hallahan, AR, Northcott, PA, Pfister, SM, Wechsler-Reya, RJ, Rusert, JM, Taylor, MD, Cho, Y-J, Packer, RJ, Brown, KJ & Rood, BR 2015, 'Proteomic profiling of high risk medulloblastoma reveals functional biology', Oncotarget, vol. 6, no. 16, pp. 14584-14595. https://doi.org/10.18632/oncotarget.3927
Staal JA, Lau LS, Zhang H, Ingram WJ, Hallahan AR, Northcott PA et al. Proteomic profiling of high risk medulloblastoma reveals functional biology. Oncotarget. 2015 Jan 1;6(16):14584-14595. https://doi.org/10.18632/oncotarget.3927
Staal, Jerome A. ; Lau, Ling San ; Zhang, Huizhen ; Ingram, Wendy J. ; Hallahan, Andrew R. ; Northcott, Paul A. ; Pfister, Stefan M. ; Wechsler-Reya, Robert J. ; Rusert, Jessica M. ; Taylor, Michael D. ; Cho, Yoon-Jae ; Packer, Roger J. ; Brown, Kristy J. ; Rood, Brian R. / Proteomic profiling of high risk medulloblastoma reveals functional biology. In: Oncotarget. 2015 ; Vol. 6, No. 16. pp. 14584-14595.
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