title: SOXC and MiR17-92 gene expression profiling defines two subgroups with different clinical outcome in mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is a heterogeneous B-cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR-17-92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL. In this study we screened the transcriptional profiles of 70 MCL patients for SOXC cluster and miR17, miR18a, miR19b and miR92a, from the miR-17-92 cluster. Gene expression analysis showed higher SOX11 and SOX12 levels compared to SOX4 (P ≤ 0.0026). Moreover we found a negative correlation between the expression of SOX11 and SOX4 (P < 0.0001). miR17-92 cluster analysis showed that miR19b and miR92a exhibited higher levels than miR17 and miR18a (P < 0.0001). Unsupervised hierarchical clustering revealed two subgroups with significant differences in relation to aggressive MCL features, such as blastoid morphological variant (P = 0.0412), nodal presentation (P = 0.0492), CD5(+) (P = 0.0004) and shorter overall survival (P < 0.0001). Together, our findings show for the first time an association between the differential expression profiles of SOXC and miR17-92 clusters in MCL and also relate them to different clinical subtypes of the disease adding new biological information that may contribute to a better understanding of this pathology. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina (ANM), Buenos Aires, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Roisman
authors.affiliation: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina (ANM), Buenos Aires, Argentina.|FUNDALEU, Buenos Aires, Argentina.
authors.forename: Fuad
authors.initials: F
authors.lastname: Huamán Garaicoa
authors.affiliation: División Patología, Instituto de Investigaciones Hematológicas, ANM, Buenos Aires, Argentina.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Metrebian
authors.affiliation: FUNDALEU, Buenos Aires, Argentina.|División Patología, Instituto de Investigaciones Hematológicas, ANM, Buenos Aires, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Narbaitz
authors.affiliation: Servicio de Patología, Hospital Italiano, Buenos Aires, Argentina.
authors.forename: Dana
authors.initials: D
authors.lastname: Kohan
authors.affiliation: Servicio de Patología, Hospital Italiano, Buenos Aires, Argentina.
authors.forename: Hernán
authors.initials: H
authors.lastname: García Rivello
authors.affiliation: FUNDALEU, Buenos Aires, Argentina.
authors.forename: Isolda
authors.initials: I
authors.lastname: Fernandez
authors.affiliation: FUNDALEU, Buenos Aires, Argentina.
authors.forename: Astrid
authors.initials: A
authors.lastname: Pavlovsky
authors.affiliation: FUNDALEU, Buenos Aires, Argentina.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pavlovsky
authors.affiliation: Patología Molecular, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España.
authors.forename: Luis
authors.initials: L
authors.lastname: Hernández
authors.affiliation: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina (ANM), Buenos Aires, Argentina.
authors.forename: Irma
authors.initials: I
authors.lastname: Slavutsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D062085:RNA, Long Noncoding; D055751:SOXC Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C097473:SOX11 protein, human; C107423:SOX12 protein, human; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors