title: Alteration of the lipid profile in lymphomas induced by MYC overexpression.
abstract: 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.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305-5080;
authors.forename: Livia S
authors.initials: LS
authors.lastname: Eberlin
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94305-5151; and.
authors.forename: Meital
authors.initials: M
authors.lastname: Gabay
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94305-5151; and.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Fan
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94305-5151; and.
authors.forename: Arvin M
authors.initials: AM
authors.lastname: Gouw
authors.affiliation: Departments of Health Research and Policy andStatistics, Stanford University, Stanford, CA 94305-4065.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tibshirani
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94305-5151; and.
authors.forename: Dean W
authors.initials: DW
authors.lastname: Felsher
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305-5080; zare@stanford.edu.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Zare
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D050356:Lipid Metabolism; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D018631:ras Proteins / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D018631:ras Proteins
keywords: biostatistics; cancer; lipidomics; metabolomics; transgenic models