Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study

Lorraine Tracey, Raquel Villuendas, Ana Maria Dotor, Inmaculada Spiteri, Pablo Ortiz, Juan F Garcia, Jose Luis Rodriguez Peralto, Mark Lawler, Miguel A Piris, Mark Lawler

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Mycosis fungoides (MF) is the most frequent type of cutaneous T-cell lymphoma, whose diagnosis and study is hampered by its morphologic similarity to inflammatory dermatoses (ID) and the low proportion of tumoral cells, which often account for only 5% to 10% of the total tissue cells. cDNA microarray studies using the CNIO OncoChip of 29 MF and 11 ID cases revealed a signature of 27 genes implicated in the tumorigenesis of MF, including tumor necrosis factor receptor (TNFR)-dependent apoptosis regulators, STAT4, CD40L, and other oncogenes and apoptosis inhibitors. Subsequently a 6-gene prediction model was constructed that is capable of distinguishing MF and ID cases with unprecedented accuracy. This model correctly predicted the class of 97% of cases in a blind test validation using 24 MF patients with low clinical stages. Unsupervised hierarchic clustering has revealed 2 major subclasses of MF, one of which tends to include more aggressive-type MF cases including tumoral MF forms. Furthermore, signatures associated with abnormal immunophenotype (11 genes) and tumor stage disease (5 genes) were identified.

Original languageEnglish
Pages (from-to)1042-50
Number of pages9
JournalBlood
Volume102
Issue number3
DOIs
Publication statusPublished - 01 Aug 2003

Keywords

  • Cluster Analysis
  • Diagnosis, Differential
  • Disease Progression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Biological
  • Mycosis Fungoides
  • Predictive Value of Tests
  • Signal Transduction
  • Skin
  • Skin Diseases
  • Tumor Necrosis Factor-alpha

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    Tracey, L., Villuendas, R., Dotor, A. M., Spiteri, I., Ortiz, P., Garcia, J. F., Peralto, J. L. R., Lawler, M., Piris, M. A., & Lawler, M. (2003). Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study. Blood, 102(3), 1042-50. https://doi.org/10.1182/blood-2002-11-3574