title: microRNA expression profiles identify subtypes of mantle cell lymphoma with different clinicobiological characteristics.
abstract: OBJECTIVE
  microRNAs (miRNA) are posttranscriptional gene regulators that may be useful as diagnostic and/or prognostic biomarkers. We aim to study the expression profiles of a high number of miRNAs and their relationship with clinicopathologic and biologic relevant features in leukemic mantle cell lymphomas (MCL).
  
  
  METHODS
  Expression profiling of 664 miRNAs was investigated using a high-throughput quantitative real-time PCR platform in 30 leukemic MCLs. Statistical and bioinformatic analyses were conducted to define miRNAs associated with different clinicopathologic parameters. Gene expression profiling was investigated by microarrays in 16 matching cases to study the potential genes and pathways targeted by selected miRNAs. The prognostic value of miR-34a was investigated in 2 independent series of 29 leukemic and 50 nodal MCLs.
  
  
  RESULTS
  Robust consensus clustering defined 2 main MCL subgroups with significant differences in the immunoglobulin (IGHV) mutational status, SOX11 expression, genomic complexity, and nodal clinical presentation. Supervised analyses of IGHV and SOX11 categories identified 17 and 22 miRNAs differentially expressed, respectively. Enriched targets of these miRNAs corresponded to relevant pathways in MCL pathogenesis such as DNA stress response, CD40 signaling, and chromatin modification. In addition, we found 7 miRNAs showing prognostic significance independently of IGHV status and SOX11 expression. Among them, miR-34a was also associated with poor prognosis in 2 independent series of leukemic and nodal MCL, and in cooperation with high expression of the MYC oncogene.
  
  
  CONCLUSIONS
  We have identified miRNAs and target pathways related to clinical and biologic variants of leukemic MCL, and validated miR-34a as a prognostic marker in MCL.
authors: Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Alba
authors: A
authors: Navarro
authors: Guillem
authors: G
authors: Clot
authors: Miriam
authors: M
authors: Prieto
authors: Cristina
authors: C
authors: Royo
authors: Maria Carmela
authors: MC
authors: Vegliante
authors: Virginia
authors: V
authors: Amador
authors: Elena
authors: E
authors: Hartmann
authors: Itziar
authors: I
authors: Salaverria
authors: Sílvia
authors: S
authors: Beà
authors: Jose Ignacio
authors: JI
authors: Martín-Subero
authors: Andreas
authors: A
authors: Rosenwald
authors: German
authors: G
authors: Ott
authors: Adrian
authors: A
authors: Wiestner
authors: Wyndham H
authors: WH
authors: Wilson
authors: Elías
authors: E
authors: Campo
authors: Luis
authors: L
authors: Hernández
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D055751:SOXC Transcription Factors / Q000096:biosynthesis*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D007136:Immunoglobulins; D035683:MicroRNAs; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors
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