A Meta-Analysis of Gene Expression Data Identifies a Molecular Signature Characteristic for Tumor-Stage Mycosis Fungoides

• Published in: Journal of investigative dermatology Vol. 132; no. 8; pp. 2050 - 2059
• Main Authors: van Kester, Marloes S., Borg, Martin K., Zoutman, Willem H., Out-Luiting, Jacoba J., Jansen, Patty M., Dreef, Enno J., Vermeer, Maarten H., van Doorn, Remco, Willemze, Rein, Tensen, Cornelis P.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2012; Nature Publishing Group; Elsevier Limited
• Subjects: ATPases Associated with Diverse Cellular Activities; Bioinformatics; Biological and medical sciences; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Cell cycle; Cell Cycle Proteins; Computational Biology - methods; Data processing; Dermatology; DNA Methylation; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; I-kappa B Proteins; Immunophenotyping; Inflammation; Interleukins - metabolism; Kinetochores; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes T; Lymphoma, T-Cell, Cutaneous - genetics; Lymphoma, T-Cell, Cutaneous - metabolism; Malignancy; Medical sciences; Models, Genetic; Mycosis fungoides; Mycosis Fungoides - genetics; Mycosis Fungoides - metabolism; NF- Kappa B protein; NF-kappa B - metabolism; Nuclear Proteins - biosynthesis; Oligonucleotide Array Sequence Analysis; Polymerase chain reaction; Proteins - genetics; Proteins - metabolism; Reviews; RNA, Messenger - metabolism; Skin; T-cell lymphoma; Tumors; Skin disease; Cutaneous hematologic disease; Characteristics; Dermatology; Lymphoproliferative syndrome; Mycosis fungoides; Tumor; Malignant hemopathy; Non Hodgkin lymphoma; Gene expression; Peripheral T cell lymphoma; Cancer
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2012.117

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.