Gene Set: HAHTOLA_MYCOSIS_FUNGOIDES_SKIN_DN

Standard name HAHTOLA_MYCOSIS_FUNGOIDES_SKIN_DN
Systematic name M5570
Brief description Genes down-regulated in lesional skin biopsies from mycosis fundoides patients compared to the normal skin samples.
Full description or abstract PURPOSE: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes. EXPERIMENTAL DESIGN: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4(+) cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression. RESULTS: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations. CONCLUSIONS: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16914566   Authors: Hahtola S,Tuomela S,Elo L,Häkkinen T,Karenko L,Nedoszytko B,Heikkilä H,Saarialho-Kere U,Roszkiewicz J,Aittokallio T,Lahesmaa R,Ranki A
Exact source Table 4S: M =< -1
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 3.0: First introduced

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