title: Genomic imbalances and microRNA transcriptional profiles in patients with mycosis fungoides.
abstract: Mycosis fungoides is the most common type of primary cutaneous T cell lymphoma. We have evaluated CDKN2A losses and MYC gains/amplifications by FISH analysis, as well as expression of miR-155 and members of the oncogenic cluster miR-17-92 (miR17, miR18a, miR19b, and miR92a) in MF patients with advanced disease. Formalin-fixed paraffin-embedded skin biopsies from 36 patients at diagnosis, 16 with tumoral MF (T-MF), 13 in histological transformation to a large T cell lymphoma (TR-MF), and 7 cases with folliculotropic variant (F-MF), were studied. Twenty cases showed genomic alterations (GAs): 8 (40 %) had CDKN2A deletion, 7 (35 %) showed MYC gain, and 5 (25 %) exhibited both alterations. GAs were more frequently observed in F-MF (p = 0.004) and TR-MF (p = 0.0001) than T-MF. GAs were significantly higher in cases presenting lesions in head, neck, and lower extremities compared to those observed in trunk and upper extremities (p = 0.03), when ≥25 % neoplastic cells were CD30 positive (p = 0.016) as well as in cases with higher Ki-67 proliferation index (p = 0.003). Patients with GAs showed bad response to treatment (p = 0.02) and short survival (p = 0.04). Furthermore, MF patients showed higher miRNA expression compared to controls (p ≤ 0.0223). T-MF showed higher miR17 and miR-18a expression compared to F-MF and TR-MF (p ≤ 0.0387) while miR19b, miR92a, and miR-155 showed increased levels in F-MF and TR-MF with respect to T-MF (p ≤ 0.0360). Increased expression of miR17 and miR19b in GA group compared to cases without alterations (p ≥ 0.0307) was also detected. Our results add new information about genomic imbalances in MF patients, particularly in F-MF, and extend the present view of miRNA deregulation in this disease.
authors.affiliation: Laboratorio de Genética de las Neoplasias Linfoides, Instituto de Medicina Experimental (IMEX), CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina.|Laboratorio de Patología, Fundaleu, C1126ABF, Peña, 2208, CABA, Argentina.|División Patología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Fuad Huaman
authors.initials: FH
authors.lastname: Garaicoa
authors.affiliation: Laboratorio de Genética de las Neoplasias Linfoides, Instituto de Medicina Experimental (IMEX), CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Roisman
authors.affiliation: Servicio de Dermatología, Hospital General de Agudos Dr. Cosme Argerich, Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Arias
authors.affiliation: Servicio de Patología, Hospital General de Agudos Dr. Cosme Argerich, Buenos Aires, Argentina.
authors.forename: Carla
authors.initials: C
authors.lastname: Trila
authors.affiliation: Servicio de Dermatología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fridmanis
authors.affiliation: Servicio de Dermatología, Hospital General de Agudos Dr. Cosme Argerich, Buenos Aires, Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Abeldaño
authors.affiliation: Laboratorio de Anatomía Patológica, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vanzulli
authors.affiliation: Laboratorio de Patología, Fundaleu, C1126ABF, Peña, 2208, CABA, Argentina.|División Patología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Narbaitz
authors.affiliation: Laboratorio de Genética de las Neoplasias Linfoides, Instituto de Medicina Experimental (IMEX), CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina. islavutsky@hematologia.anm.edu.ar.
authors.forename: Irma
authors.initials: I
authors.lastname: Slavutsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D042822:Genomic Instability; D023281:Genomics / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: FISH; Genomic alterations; Mycosis fungoides; miR-155; miR-17-92 cluster; microRNA expression