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. and Rood, Brian R. (2015) Proteomic profiling of high risk medulloblastoma reveals functional biology. Oncotarget, 6 16: 14584-14595.

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Author 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.
Title Proteomic profiling of high risk medulloblastoma reveals functional biology
Journal name Oncotarget   Check publisher's open access policy
ISSN 1949-2553
Publication date 2015-04-23
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 6
Issue 16
Start page 14584
End page 14595
Total pages 12
Place of publication Albany, NY, United States
Publisher Impact Journals
Collection year 2016
Language eng
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.
Keyword Cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
Child Health Research Centre Publications
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