Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study.
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.
Tracey
Lorraine
L
Molecular Pathology Program, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro, 3 Madrid 28029, Spain.
Villuendas
Raquel
R
Dotor
Ana Maria
AM
Spiteri
Inmaculada
I
Ortiz
Pablo
P
Garcia
Juan F
JF
Peralto
Jose Luis Rodriguez
JL
Lawler
Mark
M
Piris
Miguel A
MA
D016000:Cluster Analysis; D003937:Diagnosis, Differential; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009182:Mycosis Fungoides / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D011237:Predictive Value of Tests; D015398:Signal Transduction; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000175:diagnosis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha