title: A meta-analysis of gene expression data identifies a molecular signature characteristic for tumor-stage mycosis fungoides.
abstract: Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma (CTCL). To identify a molecular signature characteristic of MF tumor stage, we used a bioinformatic approach involving meta-analysis of publicly available gene expression data sets combined with previously generated gene expression data. Results for a selection of genes were further refined and validated by quantitative PCR and inclusion of additional controls. With this approach, we identified a profile specific for MF tumor stage, consisting of 989 aberrantly expressed genes, the majority of which (718 genes) are statistically significantly more expressed in MF compared with normal skin, inflamed skin, and normal T cells. As expected, the signature contains genes reflecting the highly proliferative characteristic of this T-cell malignancy, including altered expression of cell cycle and kinetochore regulators. We uncovered details of the immunophenotype, suggesting that MF originates from IL-32-producing cells and identified previously unreported therapeutic targets and/or diagnostic markers, for example, GTSF1 and TRIP13. Loss of expression of the NF-κB inhibitor, NFKBIZ, may partly explain the enhanced activity of NF-κB, which is a hallmark of MF and other CTCLs.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marloes S
authors.initials: MS
authors.lastname: van Kester
authors.forename: Martin K
authors.initials: MK
authors.lastname: Borg
authors.forename: Willem H
authors.initials: WH
authors.lastname: Zoutman
authors.forename: Jacoba J
authors.initials: JJ
authors.lastname: Out-Luiting
authors.forename: Patty M
authors.initials: PM
authors.lastname: Jansen
authors.forename: Enno J
authors.initials: EJ
authors.lastname: Dreef
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Vermeer
authors.forename: Remco
authors.initials: R
authors.lastname: van Doorn
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Tensen
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D018797:Cell Cycle Proteins; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020672:I-kappa B Proteins; D016130:Immunophenotyping; D007378:Interleukins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000378:metabolism*; D008957:Models, Genetic; D009182:Mycosis Fungoides / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C575258:GTSF1 protein, human; D020672:I-kappa B Proteins; C496971:IL32 protein, human; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D000074183:ATPases Associated with Diverse Cellular Activities; C575259:TRIP13 protein, human