microRNA Profiling in Blastoid Mantle Cell Lymphoma.
Wesley O Greaves, Keyur P Patel, Bedia A Barkoh, Bal M Mishra, Shen Li, Yao Hui, L Jeffrey Medeiros, Rajyalakshmi Luthra. University of Texas MD Anderson Cancer Center, Houston
Background: Mantle cell lymphoma (MCL), defined by the presence of t(11;14)(q13;q32) and cyclin D1 overexpression, can be divided histologically into classical and aggressive variants which correlate with clinical behavior. Histologically aggressive variants of MCL have been further subdivided into blastoid and pleomorphic types in the 2008 WHO classification. Aberrant miRNA expression has previously been demonstrated in MCL cell lines and patient samples. However, differential expression of miRNA in histologically aggressive variants of MCL (heretofore referred to as blastoid) has not been explored. In this study we compared the miRNA expression profiles of blastoid MCL, classical MCL and reactive lymph nodes.
Design: Total RNA, including miRNA, was isolated from paraffin-embedded biopsy specimens of 8 classical and 8 blastoid MCL (4 blastoid and 4 pleomorphic) using the RecoverAll TM Total Nucleic Acid Isolation Kit (Ambion, Inc). All cases showed cyclin D1 overexpression by immunohistochemistry. A subset of cases also showed the presence of t(11;14) by conventional cytogenetics, FISH and/or molecular studies. Seven reactive lymph node specimens were used as normal controls. A microRNA profile for each case was generated using Human miRNA Microarray Version 3 (Agilent Technologies, Santa Clara, CA). Hierarchical clustering was performed using Pearson correlation metric with Ward's linkage. Two-sample t-tests were used to identify miRNAs that were significantly differentially expressed between classic and blastoid MCL. The beta-uniform mixture model was used to control false discovery rate (FDR).
Results: Hierarchical clustering analysis identified groups defined by miRNA expression that were significantly associated with classical and blastoid variants as compared with reactive lymph nodes (P < 0.01). Two hundred and eighty four miRNAs were differentially expressed between blastoid MCL and reactive lymph nodes (FDR < 0.1). Of these, 254 miRNAs were also differentially expressed between classical MCL and reactive lymph nodes (FDR < 0.1), while 30 miRNAs were unique to the blastoid group. Differentially expressed miRNAs unique to blastoid MCL include novel miRNAs, such as miR-933, as well as others which have been previously shown to play a role in oncogenesis in other tumors, such as miR-155 and miR-149.
Conclusions: Blastoid MCL demonstrates an aberrant miRNA expression signature distinct from reactive lymphoid tissue and classical MCL, suggesting that specific miRNAs may play a role in blastoid phenotype.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 194, Wednesday Afternoon