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

13 Scopus citations

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 - 2015

Keywords

  • Cancer
  • Glycolysis
  • Medulloblastoma
  • Proteomics
  • cMYC

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Proteomic profiling of high risk medulloblastoma reveals functional biology'. Together they form a unique fingerprint.

  • Cite this

    Staal, J. A., Lau, L. S., Zhang, H., Ingram, W. J., Hallahan, A. R., Northcott, P. A., Pfister, S. M., Wechsler-Reya, R. J., Rusert, J. M., Taylor, M. D., Cho, Y. J., Packer, R. J., Brown, K. J., & 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