title: Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL).
abstract: Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Ralfkiaer
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hagedorn
authors.forename: Nannie
authors.initials: N
authors.lastname: Bangsgaard
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Løvendorf
authors.forename: Charlotte B
authors.initials: CB
authors.lastname: Ahler
authors.forename: Lars
authors.initials: L
authors.lastname: Svensson
authors.forename: Katharina L
authors.initials: KL
authors.lastname: Kopp
authors.forename: Marie T
authors.initials: MT
authors.lastname: Vennegaard
authors.forename: Britt
authors.initials: B
authors.lastname: Lauenborg
authors.forename: John R
authors.initials: JR
authors.lastname: Zibert
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.forename: Rolf
authors.initials: R
authors.lastname: Søkilde
authors.forename: Lise M
authors.initials: LM
authors.lastname: Gjerdrum
authors.forename: Tord
authors.initials: T
authors.lastname: Labuda
authors.forename: Anne-Merete
authors.initials: AM
authors.lastname: Mathiesen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbæk
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sokolowska-Wojdylo
authors.forename: Catherine
authors.initials: C
authors.lastname: Queille-Roussel
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiaer
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.forename: Christian
authors.initials: C
authors.lastname: Glue
authors.forename: Mads A
authors.initials: MA
authors.lastname: Røpke
authors.forename: Lone
authors.initials: L
authors.lastname: Skov
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D011379:Prognosis; D011565:Psoriasis / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D035683:MicroRNAs