Journal
CANCER CELL
Volume 29, Issue 1, Pages 104-116Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2015.12.004
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Funding
- Sidney Kimmel Center for Prostate and Urologic Cancers
- MSK Cancer Center [P30 CA008748]
- NIH [P30 CA125123, 5U24CA143843]
- NCI [5T32CA160001]
- MSK Center for Translational Cancer Genomic Analysis
- Jill and Jeffrey Weiss Fund
- J. Randall & Kathleen L. MacDonald Kidney Cancer Research Fund
- [U24 CA143840]
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Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort.
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