Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified.
Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK-. Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK- and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK-, respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated.
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Laginestra
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Piccaluga
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Fuligni
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Rossi
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Agostinelli
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Righi
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Sapienza
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Motta
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Gazzola
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Mannu
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Sabattini
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Bacci
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Tabanelli
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Sacchetti
Department of Pathology, São Paulo University, Medical School, São Paulo, Brazil.
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Barrese
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Etebari
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Melle
Microbiology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Clò
Microbiology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Gibellini
Tumour Immunology Unit, Department of Health Science, Human Pathology Section University of Palermo School of Medicine, Palermo, Italy.
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Tripodo
Department of Pathology and Center for Experimental Research and Medical Studies, University of Torino, Turin, Italy.
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Inghirami
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
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Croce
Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S Orsola-Malpighi Hospital, Bologna University Medical School, Bologna, Italy.
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Pileri
D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
D035683:MicroRNAs; D012334:RNA, Neoplasm