title: Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis.
abstract: miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNA classifier showed consistent results in formalin-fixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Yulei
authors.initials: Y
authors.lastname: Shen
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Cuiling
authors.initials: C
authors.lastname: Liu
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Lachel
authors.forename: Karen
authors.initials: K
authors.lastname: Deffenbacher
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Sharathkumar
authors.initials: S
authors.lastname: Bhagavathi
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Lisa
authors.initials: L
authors.lastname: Rimsza
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: James O
authors.initials: JO
authors.lastname: Armitage
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy W
authors.initials: TW
authors.lastname: McKeithan
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D057166:High-Throughput Screening Assays; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D046228:Microarray Analysis; D008875:Middle Aged; D011379:Prognosis; D054928:Validation Studies as Topic
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs