title: MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma.
abstract: MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain. Electronic address: jsandoval@idibell.cat.
authors.forename: Juan
authors.initials: J
authors.lastname: Sandoval
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Díaz-Lagares
authors.affiliation: Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Salgado
authors.affiliation: Servei de Dermatologia i Patologia, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Octavio
authors.initials: O
authors.lastname: Servitje
authors.affiliation: Servei de Dermatologia i Patologia, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Fina
authors.initials: F
authors.lastname: Climent
authors.affiliation: Servicio de Dermatologia, Hospital 12 de Octubre, University Complutense Madrid, Madrid, Spain.
authors.forename: Pablo L
authors.initials: PL
authors.lastname: Ortiz-Romero
authors.affiliation: Servicio de Dermatologia, Hospital General de Valencia, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Pérez-Ferriols
authors.affiliation: Servei de Dermatologia, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Garcia-Muret
authors.affiliation: Servei de Dermatologia, Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Estrach
authors.affiliation: Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Servei d'Anàlisi de Microarrays, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Nonell
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain; Department of Physiological Science II, School of Medicine, University of Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Servei de Dermatologia, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Pujol
authors.affiliation: Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
authors.affiliation: Servei de Dermatologia, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Electronic address: fgallardo@parcdesalutmar.cat.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gallardo
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000378:metabolism; D017731:Lymphomatoid Papulosis / Q000235:genetics / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D017730:Ki-1 Antigen; D035683:MicroRNAs