Journal Article

DKFZ-2017-03568

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Proteomic profiling of high risk medulloblastoma reveals functional biology.

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

2015
Impact Journals LLC [S.l.]

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Please use a persistent id in citations: doi:10.18632/oncotarget.3927

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(s): Biomarkers, Tumor

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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