Heterogeneity of tumor-induced gene expression changes in the human metabolic network

Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how the expression of metabolic genes in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression changes of some metabolic pathways (e.g., upregulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation) are very heterogeneous. Our analysis also suggests that the expression changes of some metabolic genes (e.g., isocitrate dehydrogenase and fumarate hydratase) may enhance or mimic the effects of recurrent mutations in tumors. On the level of individual biochemical reactions, many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes. These isoenzymes are potential targets for anticancer therapy.National Institutes of Health (U.S.) (grant GM079759)National Institutes of Health (U.S.) (NIH Pathway to Independence Award R00CA168997)National Institute of Environmental Health Sciences (Grant R01ES01931)National Centers for Biomedical Computing (U.S.) (grant U54CA121852)Ellison Medical Foundation (New Scholar award AG-NS-0577-09)Fred Hutchinson Cancer Research Center (New Development Funds)Burroughs Wellcome FundDamon Runyon Cancer Research FoundationSmith Family FoundationNational Cancer Institute (U.S.