Proteomic profiling of high risk medulloblastoma reveals functional biology
| Autor: | Ling San Lau, Andrew R. Hallahan, Kristy J. Brown, Jerome A. Staal, Stefan M. Pfister, Yoon Jae Cho, Huizhen Zhang, Paul A. Northcott, Roger J. Packer, Wendy J. Ingram, Robert J. Wechsler-Reya, Michael D. Taylor, Jessica M. Rusert, Brian R. Rood |
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| Rok vydání: | 2015 |
| Předmět: |
Proteomics
Computational biology Biology medulloblastoma Mass Spectrometry Transcriptome Risk Factors Cell Line Tumor Biomarkers Tumor medicine cancer Humans Cerebellar Neoplasms cMYC Ribonucleoprotein Medulloblastoma Genetics Proteomic Profiling Alternative splicing Cancer glycolysis medicine.disease 3. Good health Oncology Proteome Research Paper |
| Zdroj: | Oncotarget ResearcherID |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.3927 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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