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: Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine S Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia M Lachel, Karen Deffenbacher, Timothy C Greiner, Julie M Vose, Sharathkumar Bhagavathi, Louis M Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita M Braziel, James R Cook, Raymond R Tubbs, Randy D Gascoyne, James O Armitage, Dennis D Weisenburger, Timothy W McKeithan, Wing C Chan
• Journal: Blood (Blood) Vol. 119 Issue 21 Pg. 4939-48 (May 24 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22490335 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• MicroRNAs

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis, genetics, isolation & purification)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genome, Human
• High-Throughput Screening Assays
• Humans
• Lymphoma, Mantle-Cell (classification, diagnosis, genetics, mortality)
• Male
• MicroRNAs (genetics, physiology)
• Microarray Analysis
• Middle Aged
• Prognosis
• Validation Studies as Topic