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Cancer Cell. 2016 Jan 11;29(1):104-16. doi: 10.1016/j.ccell.2015.12.004.

An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.

Author information

  • 1Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Computational Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 2Computational Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 3Genitourinary Oncology Service, Department of Medicine; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 4Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • 5Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 6Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 7Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 8Metabolon Inc., Durham, NC 27713, USA.
  • 9Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 10Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 11Genitourinary Oncology Service, Department of Medicine; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: hsiehj@mskcc.org.

Abstract

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.

PMID:
26766592
PMCID:
PMC4809063
DOI:
10.1016/j.ccell.2015.12.004
[PubMed - indexed for MEDLINE]
Free PMC Article
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