Alteration of the lipid profile in lymphomas induced by MYC overexpression

Significance Desorption electrospray ionization mass spectrometric imaging (DESI-MSI) has been shown to be particularly powerful for identifying lipids and metabolites directly from tissue sections and providing a chemical map of their distribution. We applied DESI-MSI to investigate changes in lipid profiles that occur in animal and human lymphomas associated with the overexpression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC). Using statistical analysis, we found 86 lipids that were either increased or decreased in MYC-induced transgenic mouse models of lymphoma. Most of the increased lipids were glycerophosphoglycerols and cardiolipins with a higher content of monounsaturated fatty acids when compared with control tissue. The lipid profiles of MYC associated human lymphomas with overexpression of MYC resemble closely those observed in MYC-induced transgenic mouse models. Overexpression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC) oncogene is one of the most commonly implicated causes of human tumorigenesis. MYC is known to regulate many aspects of cellular biology including glucose and glutamine metabolism. Little is known about the relationship between MYC and the appearance and disappearance of specific lipid species. We use desorption electrospray ionization mass spectrometry imaging (DESI-MSI), statistical analysis, and conditional transgenic animal models and cell samples to investigate changes in lipid profiles in MYC-induced lymphoma. We have detected a lipid signature distinct from that observed in normal tissue and in rat sarcoma-induced lymphoma cells. We found 104 distinct molecular ions that have an altered abundance in MYC lymphoma compared with normal control tissue by statistical analysis with a false discovery rate of less than 5%. Of these, 86 molecular ions were specifically identified as complex phospholipids. To evaluate whether the lipid signature could also be observed in human tissue, we examined 15 human lymphoma samples with varying expression levels of MYC oncoprotein. Distinct lipid profiles in lymphomas with high and low MYC expression were observed, including many of the lipid species identified as significant for MYC-induced animal lymphoma tissue. Our results suggest a relationship between the appearance of specific lipid species and the overexpression of MYC in lymphomas.

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