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

Blood. 2003 Aug 1;102(3):1042-50. doi: 10.1182/blood-2002-11-3574. Epub 2003 Apr 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Tumor Necrosis Factor-alpha